JP2016006102A - Oral care product and method of use and manufacture thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To use an improved preservative in mouthwash containing a basic amino acid.SOLUTION: The invention relates to a mouthwash comprising an aqueous solution of an effective amount of a basic amino acid, in free or salt form together with an effective amount of a preservative selected from methylisothiazolinone (MIT), benzyl alcohol, phenoxyethanol, and combinations thereof; as well as to methods of using and of making such compositions.

Description

  The present invention relates to an oral cleanser containing a free or salt basic amino acid and a preservative selected from methylisothiazolinone, benzyl alcohol, phenoxyethanol and combinations thereof, and methods of using and making these compositions About.

  Due to the high water content, it is particularly difficult for oral cleaners to prevent microbial contamination. Arginine and other basic amino acids have been proposed for use in oral care and are thought to be of great help in combating cavitation and dental sensitivity, but oral cleansing agents containing arginine or basic amino acids Tends to have a basic pH and is more difficult to formulate in an oral cleanser because of the higher likelihood of microbial contamination compared to acidic formulations. Furthermore, not all preservatives are active at high pH. Some preservatives have a negative effect on the taste or aesthetics of the product. Certain preservatives such as ethanol or parabens are known to be effective at various pHs, but these preservatives are not suitable for all products or products.

  Accordingly, there is a need for improved preservatives for use in oral cleansing agents that contain basic amino acids.

  Surprisingly here, oral cleansing agents containing a basic amino acid such as free or salt arginine and a preservative selected from methylisothiazolinone, benzyl alcohol, phenoxyethanol and combinations thereof are stable and effective I discovered that.

  In one embodiment, the mouth rinse further comprises an anionic polymer and / or pyrophosphate.

  Accordingly, the present invention provides an oral care composition that is effective in inhibiting or reducing plaque accumulation, reducing the level of acid-producing (cariogenic) bacteria, remineralizing teeth, and inhibiting or reducing gingivitis. Includes methods of using the oral care composition. The present invention also promotes systemic health, including cardiovascular health, to clean the oral cavity and reduce oral health and / or the likelihood of systemic infection via, for example, oral tissue It includes compositions and methods for providing improved methods.

Therefore, the present invention
i. An effective amount of a free or salt basic amino acid, for example, arginine;
ii. An oral cleansing composition (the composition of the present invention) is provided comprising an effective amount of an aqueous solution of a preservative selected from methylisothiazolinone (MIT), benzyl alcohol, phenoxyethanol and combinations thereof.

  The compositions of the present invention can be, for example, water, surfactants, solvents, vitamins, minerals, polymers, enzymes, wetting agents, thickeners, additional antimicrobial agents, additional preservatives, flavoring agents, coloring agents and / or Additional components selected from one or more of those combinations may be included. In certain embodiments, the present invention provides an anticalculus agent, such as an alkaline, eg, sodium or potassium salt type, eg, a polyphosphate, eg, pyrophosphate, tripolyphosphate or hexametaphosphate. And / or synthesis of maleic anhydride or maleic anhydride or a 1: 4 to 4: 1 copolymer of maleic anhydride and another polymerizable ethylenically unsaturated monomer, such as a copolymer of methyl vinyl ether / maleic anhydride An anionic polymeric polycarboxylate may be included.

  Effective amounts of individual or combined preservatives in the compositions of the present invention are, for example, as follows: MIT: less than 0.05%, for example 0.0005-0.03%, for example 0 0.001 to 0.01%, benzyl alcohol: less than 0.5%, such as 0.05 to 0.25%, such as 0.1%; or phenoxyethanol: less than 1%, such as 0.1 to 0.00. 7%.

  The invention further provides (i) reduction or inhibition of caries formation, (ii) enamel pre-cariogenic lesions detected by, for example, light-induced quantitative fluorescence (QLF) or electrical caries measurement (ECM) (Iii) reduction or inhibition of tooth demineralization and promotion of tooth remineralization, (iv) reduction of tooth sensitivity, (v) reduction or inhibition of gingivitis, (vi) ) Accelerated healing of oral ulcers or cuts, (vii) reduced levels of acid producing bacteria, (viii) increased relative levels of arginine degrading bacteria, (ix) inhibition of microbial biofilm formation in the oral cavity, (x) Raising and / or maintaining plaque pH to a level of at least pH 5.5 after glucose load, (xi) reducing plaque accumulation, (xii) treating, alleviating or reducing dry mouth, (xiii) teeth and oral Cleansing, (xiv) reduced erosion, (xv) tooth whitening, (xvi) dental immunity against cariogenic bacteria, and / or (xvii) reduced likelihood of systemic infection via, for example, oral tissue A method comprising applying an effective composition for oral application, e.g. oral rinse, optionally in combination with brushing, for promoting general health, including cardiovascular health .

Therefore, the present invention provides the following in the first embodiment:
i. An effective amount of free or salt basic amino acids,
ii. An effective amount of a preservative selected from methylisothiazolinone (MIT), benzyl alcohol, phenoxyethanol and combinations thereof;
An oral cleanser (composition 1.0) comprising an aqueous solution of, for example, any of the following compositions is provided:
1.0.1. Composition 1.0, wherein the basic amino acid is arginine, lysine, serine, citrulline, ornithine, creatine, histidine, diaminobutanoic acid, diaminopropionic acid, salts thereof and / or combinations thereof.
1.0.2. Composition 1.0 or 1.0.1 wherein the basic amino acid has the L-configuration.
1.0.3. Any of the above compositions are provided in the form of a di- or tri-peptide comprising a basic amino acid or salt thereof.
1.0.4. Any of the preceding compositions, wherein the basic amino acid is arginine.
1.0.5. Any of the preceding compositions, wherein the basic amino acid is L-arginine.
1.0.6. Any of the preceding compositions, wherein the basic amino acid is partially or wholly in salt form.
1.0.7. Composition 1.0.6 wherein the basic amino acid is arginine phosphate.
1.0.8. Composition 1.0.6 wherein the basic amino acid is arginine hydrochloride.
1.0.9. Composition 1.0.6 wherein the basic amino acid is arginine bicarbonate.
1.0.10. Any of the preceding compositions, wherein the basic amino acid is ionized by neutralization with an acid or acid salt.

1.0.11. The basic amino acid is present in an amount corresponding to 0.01 to 2% of the total composition weight, for example 0.1% to 1%, for example 0.8%, and the weight of the basic amino acid is the free base Any of the above compositions calculated as a mold.
1.0.12. Any of the preceding compositions, wherein the preservative is present in an amount such as:
i. MIT: less than 0.05%, for example 0.0005 to 0.03%, for example 0.001 to 0.01%;
ii. Benzyl alcohol: less than 0.5%, such as 0.05-0.25%, such as 0.1%; and / or iii. Phenoxyethanol: less than 1%, for example 0.1-0.7%.
1.0.13. Any of the preceding compositions, wherein the preservative comprises a combination of MIT and benzyl alcohol.
1.0.14. Said composition wherein the preservative comprises 0.01% MIT and 0.1% benzyl alcohol or the preservative comprises 0.001% MIT and 0.1% benzyl alcohol.
1.0.15. For example, an anticalculus agent, such as a salt form, for example a sodium salt form or a potassium salt form, such as pyrophosphate, tripolyphosphate or hexametaphosphate, in an amount of 0.1 to 3% Any of the above compositions comprising.
1.0.16. The anticalculus agent is, for example, a pyrophosphate selected from tetrasodium pyrophosphate and tetrapotassium pyrophosphate and mixtures thereof in an amount sufficient to provide at least 1%, 1-3% by weight of pyrophosphate ions. A said composition.
1.0.17. Tetrasodium pyrophosphate 0.1 to 1% and tetrapotassium pyrophosphate 1 to 2%, for example, 0.25 to 0.75% tetrasodium pyrophosphate and 1.0 to 1.5% tetrapotassium pyrophosphate, Said composition.
1.0.18. Polymers such as polyethylene glycol; synthetic anionic polymeric polycarboxylates such as polyvinyl methyl ether maleic acid copolymers; polysaccharides such as cellulose derivatives such as carboxymethyl cellulose or polysaccharide gums such as xanthan gum, gellan gum or carrageenan gum; Any of the preceding compositions comprising at least one polymer selected from acrylates and combinations thereof.
1.0.19. Any of the preceding compositions comprising synthetic anionic polymeric polycarboxylate, for example in an amount of 1-10%, such as 2.5-7.5%.
1.0.20. Synthetic anionic polymeric polycarboxylates from 1: 4 to 4: 1 copolymers of maleic anhydride or maleic acid and another polymerizable ethylenically unsaturated monomer, such as from a molecular weight (M.W.) of 30,000 Said composition being methyl vinyl ether / maleic anhydride having 5,000,000 daltons, for example 500 kD to 3000 kD.

1.0.21. General structure _{- [- CH 2 -CH (OCH} 3) -CH (COOH) -CH (COOH) -] comprising a copolymer of methyl vinyl ether / maleic anhydride having _n, the composition.
1.0.22. CP at 25 ° C. has a viscosity of 1 to ³ kCP, for example 1.7 × 10 ³ CP, nominal molecular weight is 500 kD to 3000 kD, for example 1.98 × 10 ⁶ , for example 1 to 10 Said composition in an amount of% by weight, for example 5% by weight.
1.0.23. Any of the preceding compositions wherein the composition does not comprise ethanol.
1.0.24. For example, it further comprises a soluble calcium salt selected from calcium glycerophosphate and soluble carboxylic acid salts and mixtures thereof, for example, calcium salt is calcium citrate, calcium malate, calcium lactate, calcium formate, calcium fumarate, gluconic acid Any of the preceding compositions selected from calcium, calcium lactate gluconate, calcium aspartate and calcium propionate and mixtures thereof.
1.0.25. Fluorine source, eg, fluoride salt, eg, sodium fluoride, or fluoride salt in which fluorine is covalently bonded to another atom, eg, monofluorophosphate, eg, sodium monofluorophosphate, fluorosilicic acid Any of the preceding compositions further comprising a salt, such as sodium fluorosilicate or ammonium fluorosilicate, or a fluorosulfate, such as hexafluorosulfate, fluorinated amine, and combinations thereof.
1.0.26. Said composition wherein the fluoride salt is present in an amount that provides 100 to 250 ppm of available fluorine.
1.0.27. Any of the preceding compositions comprising sodium fluoride in an amount of 0.01-0.1%, for example 0.05%.
1.0.28. Any of the preceding compositions, wherein the pH is between 7 and 9, for example 8 to 8.5, for example 8.3.
1.0.29. Any of the above compositions, for example, wherein the pH is adjusted using a weak organic acid, eg, citric acid.
1.0.30. Any of the preceding compositions further comprising an abrasive or particulate.

1.0.31. For example, poloxamer (eg, poloxamer 407), polysorbate (eg, polysorbate 20), polyoxyl hydrogenated castor oil (eg, polyoxyl 40 hydrogenated castor oil) in an amount of 0.5-5%, eg, 1-2%. And any of the preceding compositions comprising a nonionic surfactant selected from mixtures thereof.
1.0.32. Any of the preceding compositions comprising at least one wetting agent.
1.0.33. Any of the preceding compositions comprising, for example, 10-40% of the total amount of at least one wetting agent selected from glycerin, sorbitol, propylene glycol and combinations thereof.
1.0.34. Any of the preceding compositions comprising a polymer film.
1.0.35. Any of the preceding compositions comprising a flavoring, flavoring and / or coloring agent.
1.0.36. Any of the preceding compositions comprising at least 50% water.
1.0.37. Halogenated diphenyl ethers (eg, triclosan), herb extracts and essential oils (eg, rosemary extract, tea extract, magnolia extract, thymol, menthol, eucalyptol, geraniol, carvacrol, citral, hinokitiol, Catechol, methyl salicylate, epigallocatechin gallate, epigallocatechin, gallic acid, miswak extract, sea-backthorne extract), bisguanide disinfectant (eg, chlorhexidine, alexidine or octenidine), Quaternary ammonium compounds (for example, cetylpyridinium chloride (CPC), benzalkonium chloride, tetradecylpyridinium chloride (TPC), N-tetradecyl-4-ethylpyridinium Chloride (TDEPC)), phenolic antiseptics, hexetidine, octenidine, sanguinarine, povidone iodine, delmopinol, salifluor, metal ions (eg, zinc salts such as zinc citrate, stannous salts, copper salts, iron salts), sanguinarine , Propolis and oxygen additives (eg hydrogen peroxide, buffered sodium peroxyborate or sodium peroxycarbonate), phthalic acid and its salts, monoperthalic acid and its salts and esters, ascorbyl stearate, Oleoyl sarcosine, alkyl sulfate, dioctyl sulfosuccinate, salicylanilide, domifene bromide, delmopinol and octapinol and other piperidino derivatives, nisin preparation, chlorite Is selected from mixtures of any of the pre comprising said additional antimicrobial agent, any of the compositions.
1.0.38. Any of the preceding compositions comprising, for example, an antioxidant selected from the group consisting of coenzyme Q10, PQQ, vitamin C, vitamin E, vitamin A, BHT, anethole-dithiothione and mixtures thereof.
1.0.39. Any of the preceding compositions comprising a brightener.
1.0.40. A whitening agent selected from a whitening active selected from the group consisting of peroxides, metal chlorites, perborates, percarbonates, peroxy acids, hypochlorites, and combinations thereof; Any of the above compositions comprising.

1.0.41. Hydrogen peroxide or a source of hydrogen peroxide, such as urea peroxide or peroxide salts or complexes (for example, peroxide phosphate, carbonate carbonate, perborate, peroxysilicate or persulfate, etc. Any of the preceding compositions further comprising a hydrogen peroxide polymer complex, such as calcium peroxyphosphate, sodium perborate, sodium carbonate peroxide, sodium peroxyphosphate and potassium persulfate) or hydrogen peroxide-polyvinylpyrrolidone polymer complex .
1.0.42. Any of the preceding compositions further comprising an agent that interferes with or prevents bacterial attachment, such as ELA or chitosan.
1.0.43. Any of the preceding compositions further comprising a physiologically acceptable potassium salt, such as potassium nitrate or potassium chloride, in an amount effective to reduce dental sensitivity.
1.0.44. Any of the preceding compositions comprising 0.01% to 1% of a physiologically acceptable potassium salt, such as potassium nitrate and / or potassium chloride.
1.0.45. (I) reducing or inhibiting the formation of caries, (ii) reducing, repairing or repairing enamel pre-cariogenic lesions detected by, for example, light-induced quantitative fluorescence (QLF) or electrical caries measurement (ECM) Inhibition, (iii) reducing or inhibiting tooth demineralization and promoting tooth remineralization, (iv) reducing tooth supersensitivity, (v) reducing or inhibiting gingivitis, (vi) oral ulcers or Accelerated healing of cuts, (vii) reduced levels of acidogenic bacteria, (viii) increased relative levels of arginine degrading bacteria, (ix) inhibition of microbial biofilm formation in the oral cavity, (x) after sugar loading Raising and / or maintaining plaque pH to a level of at least pH 5.5, (xi) reducing plaque accumulation, (xii) treating, alleviating or reducing dry mouth, (xiii) cleaning teeth and mouth, (xiv) ) Reduced diet, (xv) prevention of staining and / or whitening of teeth, (xvi) immunity of teeth against cariogenic bacteria, and / or (xvii) possibility of systemic infection via, for example, oral tissue Any of the above compositions effective for application to the oral cavity to promote general health, including cardiovascular health, by, for example, rinsing, optionally in combination with brushing.
1.0.46. A composition obtained or obtainable by combining with the ingredients described in any of the preceding compositions.

  The level of active ingredient will vary based on the nature of the delivery system and the particular active substance. For example, basic amino acids may be present at a level of, for example, 0.1 to 5% by weight (expressed as the weight of the free base), for example, 0.1 to 3% by weight. Fluorine may be present, for example, at a level of 25 to 250 ppm, or up to 10 times higher for professional or prescription treatment products. The level of antimicrobial agent will vary as well depending on the drug used. For example, the triclosan mouthwash may contain 0.03% by weight of triclosan, for example.

In another embodiment, the present invention is a method for improving oral health, wherein an effective amount of the oral composition of any of the previous embodiments is applied to the oral cavity of a subject in need thereof. A method comprising, for example,
i. To reduce or inhibit the formation of phagocytosis,
ii. For example, to reduce, repair or inhibit early enamel lesions detected by light-induced quantitative fluorescence (QLF) or electrical caries measurement (ECM)
iii. To reduce or inhibit tooth demineralization and promote tooth remineralization,
iv. To reduce tooth supersensitivity,
v. To reduce or inhibit gingivitis,
vi. To promote healing of ulcers or cuts in the mouth,
vii. To reduce the level of acidogenic bacteria,
viii. To increase the relative level of arginine degrading bacteria,
ix. In order to inhibit microbial biofilm formation in the oral cavity,
x. To raise and / or maintain plaque pH after sugar loading to a level of at least pH 5.5,
xi. To reduce plaque accumulation,
xii. To treat dry mouth,
xiii. For example, to enhance systemic health, including cardiovascular health, by reducing the likelihood of systemic infection via oral tissue,
xiv. To whiten teeth,
xv. To reduce tooth erosion,
xvi. To immunize (or protect) teeth against cariogenic bacteria and their effects, and / or xvii. Includes methods for cleaning teeth and oral cavity.

  The present invention further includes the use of methylisothiazolinone, benzyl alcohol, phenoxyethanol and combinations thereof in the manufacture of the compositions of the present invention, eg, for use in any of the indications described in the methods above.

Basic amino acids Basic amino acids that can be used in the compositions and methods of the present invention include not only naturally occurring basic amino acids such as arginine, lysine and histidine, but also carboxyl and amino groups in the molecule. Any basic amino acid that is water soluble and forms an aqueous solution with a pH of 7 or higher is included.

  Thus, basic amino acids include, but are not limited to, arginine, lysine, serine, citrulline, ornithine, creatinine, histidine, diaminobutanoic acid, diaminopropionic acid, salts thereof or combinations thereof. In certain embodiments, the basic amino acid is selected from arginine, citrulline and ornithine.

  In certain embodiments, the basic amino acid is arginine, such as L-arginine or a salt thereof.

  The compositions of the present invention are for topical use in the mouth, and therefore salts for use in the present invention should be safe for such use in the amounts and concentrations provided. It is. Suitable salts include salts that are known in the art to be pharmaceutically acceptable salts and are generally considered physiologically acceptable in the amounts and concentrations provided. It is. Physiologically acceptable salts include salts obtained from pharmaceutically acceptable inorganic or organic acids or bases, such as acid addition salts formed with acids that form physiologically acceptable anions, For example, from hydrogen chloride or bromide salts and base addition salts formed by bases that form physiologically acceptable cations, such as alkali metals such as potassium and sodium or alkaline earth metals such as calcium and magnesium The resulting salt is included. Physiologically acceptable salts can be prepared by reacting a sufficiently basic compound, such as an amine, with a suitable acid that provides a physiologically acceptable anion, using standard techniques known in the art. Can be obtained.

  Fluoride ion source: The oral care composition may further comprise one or more fluoride ion sources, such as soluble fluoride salts. A wide variety of fluoride ion generating materials can be used as a source of soluble fluorine in the compositions of the present invention. Examples of suitable fluoride ion generating materials are described in Briner et al., Incorporated herein by reference. U.S. Pat. No. 3,535,421, Parran, Jr. et al. U.S. Pat. No. 4,885,155 and Wilder et al. U.S. Pat. No. 3,678,154. Typical fluoride ion sources include, but are not limited to, stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, fluoride. Ammonium fluoride and combinations thereof. In certain embodiments, the fluoride ion source includes stannous fluoride, sodium fluoride, sodium monofluorophosphate, and mixtures thereof. If the formulation includes a calcium salt, the fluoride salt is a different atom than fluorine, for example in sodium monofluorophosphate, rather than simply ionically bound, as in sodium fluoride. A salt covalently bonded to is preferable.

Surfactants The present invention, in some embodiments, is an anionic surfactant, such as a water soluble salt of a higher fatty acid monoglyceride monosulfate, such as a sodium salt of a monosulfated monoglyceride of a hydrogenated coconut oil fatty acid, such as N-methyl N-methyl N-cocoyl taurate, sodium cocomo-glyceride sulfate; higher alkyl sulfates such as sodium lauryl sulfate; for example, the formula CH ₃ (CH _{2) m CH 2 (OCH 2} CH 2) n OSO 3 X ( wherein, m is 6-16, for example, a 10, n is 1-6, for example, 2, 3 or 4, X is Na Or higher alkyl-ether sulfate) Higher alkyl aryl sulfonic acids such as sodium laureth-2 sulfate (CH ₃ (CH ₂ ) ₁₀ CH ₂ (OCH ₂ CH ₂ ) ₂ OSO ₃ Na); sodium dodecyl benzene sulfonate (sodium lauryl benzene sulfonate) Salts; higher alkyl sulfoacetates such as sodium lauryl sulfoacetate (sodium dodecyl sulfoacetate), higher fatty acid esters of 1,2 dihydroxypropane sulfonate, sulfocolaurate (N-2-ethyllaurate potassium sulfoacetamide) and Contains sodium lauryl sarcosinate. “Higher alkyl” means, for example, C _6-30 alkyl. In certain embodiments, the anionic surfactant (if present) is selected from sodium lauryl sulfate and sodium lauryl sulfate ether. When present, the anionic surfactant is present in an effective amount, eg,> 0.001% by weight of the formulation, but at a concentration that does not irritate the oral tissue, eg, 1%, the optimal concentration being the specific formulation Depending on the product and the specific surfactant. In one embodiment, the anionic surfactant is present at 0.03% to 0.5% by weight, such as 0.15% by weight.

  In another embodiment, cationic surfactants useful in the present invention include lauryltrimethylammonium chloride, cetylpyridinium chloride, cetyltrimethylammonium bromide, diisobutylphenoxyethyldimethylbenzylammonium chloride, coconut alkyltrimethylammonium nitrite, cetylpyridinium fluoride and It can be broadly defined as a derivative of an aliphatic quaternary ammonium compound having one long alkyl chain containing 8 to 18 carbon atoms, such as a mixture thereof. Exemplary cationic surfactants are described in Briner et al., Incorporated herein by reference. Quaternary ammonium fluoride as described in US Pat. No. 3,535,421. Certain cationic surfactants can also act as fungicides in the composition.

  Exemplary nonionic surfactants that can be used in the compositions of the present invention condense alkylene oxide groups (hydrophilic in nature) with hydrophobic organic compounds that may be aliphatic or alkylaromatic in nature. Can be roughly defined as a compound produced. Examples of suitable nonionic surfactants include, but are not limited to, pluronics, polyethylene oxide condensates of alkylphenols, products obtained from the condensation of polyethylene oxide and ethylenediamine reaction products with ethylene oxide, aliphatic alcohols Ethylene oxide condensates, long chain tertiary amine oxides, long chain tertiary phosphine oxides, long chain dialkyl sulfoxides and mixtures of such materials. In certain embodiments, the compositions of the present invention include poloxamers (eg, poloxamer 407), polysorbates (eg, polysorbate 20), polyoxyl hydrogenated castor oil (eg, polyoxyl 40 hydrogenated castor oil) and mixtures thereof. A non-ionic surfactant selected is included.

  In certain embodiments, zwitterionic synthetic surfactants useful in the present invention can be broadly described as derivatives of aliphatic quaternary ammonium, phosphonium and sulfonium compounds, where the aliphatic radical is linear or branched. One of the aliphatic substituents contains 8 to 18 carbon atoms, and one is an anionic water-soluble group such as a carboxy group, a sulfonic acid group, a sulfuric acid group, a phosphoric acid group or a phosphonic acid group. Containing.

  Illustrative examples of surfactants suitable for inclusion in the composition include, but are not limited to, sodium alkyl sulfate, sodium lauroyl sarcosinate, cocoamidopropyl betaine and polysorbate 20 and combinations thereof.

  Surfactant or a mixture of compatible surfactants is 0.1% to 5% by weight of the total composition in the composition of the present invention, and in another embodiment 0.3% to 3% by weight. , And in other embodiments, from 0.5 wt% to 2 wt%.

Flavoring Agent The oral care composition of the present invention may also contain a flavoring agent. Flavoring agents used in the practice of the present invention include, but are not limited to, essential oils and various flavoring aldehydes, esters, alcohols and similar materials, and sweetening agents such as sodium saccharin. Examples of essential oils include spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit and orange oils. Chemicals such as menthol, carvone and anethole are also useful. In certain embodiments, peppermint and spearmint oils are used.

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

Chelating Agents and Anticalculus Agents The oral care compositions of the present invention may also optionally include one or more chelating agents that can form complexes with calcium found in the bacterial cell wall. This calcium binding weakens the bacterial cell wall and enhances bacterial lysis.

  Another group of agents suitable for use as chelating or anticalculus agents in the present invention are soluble pyrophosphates. The pyrophosphate used in the composition of the present invention may be any alkali metal pyrophosphate. In certain embodiments, the salts include 4 alkyl metal pyrophosphates, 2 alkali metal diacid pyrophosphates, 3 alkali metal monoacid pyrophosphates and mixtures thereof, wherein the alkali metal is sodium or potassium . Salts are useful in both hydrated and non-hydrated forms. An effective amount of pyrophosphate useful in the compositions of the present invention is generally sufficient to provide at least 0.5 wt% pyrophosphate ions, 0.9-3 wt%.

  Pyrophosphate also contributes to storage of the composition by reducing water activity.

Polymer The oral care composition of the present invention also includes one or more of polyethylene glycol, polyvinyl methyl ether maleic acid copolymer, polysaccharides (eg, cellulose derivatives such as carboxymethyl cellulose or polysaccharide gums such as xanthan gum or carrageenan gum) Multiple polymers are optionally included. Acidic polymers such as polyacrylic acid gels may be provided in the form of free acids or in the form of partially or fully neutralized water-soluble alkali metal (eg, potassium and sodium) or ammonium salts. .

  In certain embodiments, the composition of the present invention comprises a maleic anhydride or a 1: 4 to 4: 1 copolymer of maleic anhydride and another polymerizable ethylenically unsaturated monomer, preferably a molecular weight (M.W. .) Synthetic anionic polymeric polycarboxylates such as methyl vinyl ether / maleic anhydride having 30,000 to 3,000,000, most preferably 30,000 to 800,000 are included. These copolymers are described, for example, by ISP Technologies, Inc. , Bound Brook, N .; J. et al. Available as Gantrez available from 08805, for example, AN139 (MW 500,000), AN119 (MW 250,000) and S-97 pharmaceutical grade (MW 700,000) is there. If present, the enhancer is present in an amount of 1 to 10% by weight.

  Other treatment polymers include a 1: 1 copolymer of maleic anhydride and ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone or ethylene (the latter is described, for example, by Monsanto EMA No. 1103, M.M. W. 10,000 and EMA Grade 61) and 1: 1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone, etc. Polymer is included.

  Generally suitable is a polymerized olefinic or ethylenically unsaturated carboxylic acid containing an activated carbon-carbon olefinic double bond and at least one carboxyl group, i.e. its presence in the monomer molecule is a carboxyl group. Is an acid containing an olefinic double bond that functions easily in polymerization because it is alpha-beta in relation to or part of the terminal methylene group. Examples of such acids include acrylic acid, methacrylic acid, ethacrylic acid, alpha-chloroacrylic acid, crotonic acid, beta-acryloxypropionic acid, sorbic acid, alpha-chlorosorbic acid, cinnamic acid, beta-styrylacrylic. Acid, muconic acid, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, alpha-phenylacrylic acid, 2-benzylacrylic acid, 2-cyclohexylacrylic acid, angelic acid, umberic acid, fumaric acid, maleic acid and There is an anhydride. Other different olefinic monomers that can be copolymerized with such carboxylic monomers include vinyl acetate, vinyl chloride, dimethyl maleate, and the like. The copolymer contains sufficient carboxylate groups for water solubility.

Other types of polymeric agents include compositions containing substituted acrylamide homopolymers and / or homopolymers of unsaturated sulfonic acids and their salts, which are incorporated herein by reference. Acrylamide alican sulfones such as 2-acrylamido-2-methylpropane sulfonic acid having a molecular weight of 1,000 to 2,000,000 described in Zahid, US Pat. No. 4,842,847, Jun. 27, 1989. This is the case based on unsaturated sulfonic acids selected from acids.
Another useful class of polymeric agents includes polyamino acids, particularly Sikes et al., Incorporated herein by reference. US Pat. No. 4,866,161, which contains certain amounts of anionic surfactant amino acids such as aspartic acid, glutamic acid and phosphoserine.

  In preparing oral care compositions, it is sometimes necessary to add some thickening material to provide the desired consistency or to stabilize or enhance the performance of the formulation. In certain embodiments, the thickening agent is a water-soluble salt of a cellulose ether such as carboxyvinyl polymer, carrageenan, hydroxyethylcellulose and sodium carboxymethylcellulose and sodium carboxymethylhydroxyethylcellulose. Natural rubbers such as karaya, gum arabic and tragacanth can also be incorporated. To further improve the texture of the composition, colloidal magnesium aluminum silicate or ultrafine silica can be used as a component of the thickening composition. In certain embodiments, thickeners in an amount of about 0.5% to about 5% by weight of the total composition are used.

Enzymes The oral care composition of the present invention may also optionally include one or more enzymes. Useful enzymes include any of the available proteases, glucanohydrolases, endoglycosidases, amylases, mutanases, lipases and mutinases, or compatible mixtures thereof. In certain embodiments, the enzymes are proteases, dextranases, endoglycosidases and mutanases. In another embodiment, the enzyme is papain, endoglycosidase or a mixture of dextranase and mutanase. Additional enzymes suitable for use in the present invention are described by Ring et al. US Patent No. 5,000,939, US Patent No. 4,992,420; US Patent No. 4,355,022; US Patent No. 4,154,815; US Patent No. 4,058,595 U.S. Pat. No. 3,991,177; and U.S. Pat. No. 3,696,191, all of which are incorporated herein by reference. One enzyme of several compatible enzyme mixtures in the present invention is 0.002% to 2.0% in one embodiment, or 0.05% to 1.5% in another embodiment, or yet another In the embodiment, it constitutes 0.1% to 0.5%.

Water Water is present in the oral composition of the present invention. The water used in the preparation of commercial oral compositions should be deionized and should not contain organic impurities. Water usually accounts for the rest of the composition and constitutes 10 to 90%, for example about 40 to 70% by weight of the oral composition. This amount of water includes free water added in addition to the amount introduced with other materials such as sorbitol or any of the ingredients of the present invention.

Humectants In certain embodiments of the oral composition, it may also be desirable to incorporate a humectant that reduces evaporation and contributes to storage by reducing water activity. Certain wetting agents can also impart the desired sweetness or flavor to the composition. The wetting agent generally comprises from 15 to 70% by weight of the composition in one embodiment, or from 30 to 65% in another embodiment, based on pure wetting agent.

  Suitable wetting agents include edible polyhydric alcohols such as glycerin, sorbitol, xylitol, propylene glycol, and other polyols and mixtures of these wetting agents. Mixtures of glycerin and sorbitol may be used as a wetting agent component of the compositions herein in certain embodiments.

  The composition of the invention, in its method aspect, involves applying a safe and effective amount of the composition described herein to the oral cavity.

  The compositions and methods according to the invention protect teeth by promoting restoration and remineralization, in particular to reduce or inhibit the formation of caries, reduce or inhibit dental demineralization, Promotes oxidization, reduces tooth sensitivity, reduces, repairs or inhibits early enamel lesions as detected, for example, by light-induced quantitative fluorescence (QLF) or electrophagocytosis (ECM) Useful for methods.

  The light-induced quantitative fluorescence method is a visible fluorescence method that can detect early lesions and monitor progression or regression over a long period of time. Normal teeth fluoresce in visible light, while decalcified teeth do not emit light or only to a lesser extent. The decalcification area can be quantified and the progress monitored. Blue laser light is used to automatically light the teeth. The decalcified area has low fluorescence and appears dark compared to a healthy tooth surface. Software is used to quantify fluorescence from areas / solids associated with white spots or lesions. In general, subjects with white spot lesions are recruited as panelists. Measurements are performed on actual teeth in vivo. The lesion area / solid is measured at the start of clinical practice. Lesion area / solid reduction (improvement) is measured at the end of 6 months using the product. Data is often reported as a percentage improvement over the baseline.

  Electrical caries measurement is a technique used to measure the mineral content of teeth based on electrical resistance. Conductivity measurements take advantage of the fact that tubules filled with fluid after decalcification and enamel erosion conduct electricity. If the tooth loses its mineral content, the porosity increases and the resistance to current decreases. Therefore, an increase in the electrical conductivity of the patient's teeth can be used as an indicator of demineralization. In general, studies on root surfaces where lesions are present have been conducted. Measurements are performed on actual teeth in vivo. There is a change in electrical resistance before and 6 months after treatment. In addition, a classic phagocytic score of the root surface is performed using a probe. Hardness is classified as a three-level rating, hard, leathery or soft. In this type of study, the results are usually reported as an improvement in lesion stiffness based on ECM-measured electrical resistance (higher numbers are better) and probe scores.

  The method described in US Pat. No. 5,589,159, the entire disclosure of which is incorporated herein by reference, is used to test the properties of the compositions described herein that reduce hypersensitivity. doing. This method measures the water conductivity of the material and results in an objective drop in fluid flow that correlates to the drop in fluid flow in the tubule. In this method, a complete human molar without caries and restoration is cut perpendicular to the long axis of the tooth with a metallurgical saw and is about 0.4 to about 0.8 mm thick. Form sections or discs. Sections containing dentin but no enamel were selected for testing and then etched with a citric acid solution to remove the smear layer. J. J., a particularly airtight chamber in which each disk is connected to a pressurized liquid reservoir containing tissue culture medium. Dent. Place in a split-chambered device described in Research, 57: 187 (1978). By using a mixture of pressurized nitrogen and carbon dioxide gas, the liquid can be brought to a physiological pH. For further accuracy, the disc is moistened with artificial saliva (phosphate buffered saline, PBS) to approximately the same as the oral conditions. The device includes a glass capillary attached to a flow sensor (FLODEC, DeMarco Engineering SA, Geneva). Bubbles are injected into the glass capillary. By measuring bubble displacement as a function of time, fluid flow through the dentin disc can be measured. Fluid flow is equivalent to dentin permeability.

  Accordingly, the compositions of the present invention are in a method of reducing early enamel lesions (as measured by QLF or ECM) compared to compositions lacking an effective amount of fluorine and / or arginine. Useful.

  The composition of the present invention further comprises a method for reducing harmful bacteria in the oral cavity, such as a method for reducing or inhibiting gingivitis, a method for reducing the level of acid producing bacteria, a method for increasing the relative level of arginine degrading bacteria. , Methods for inhibiting microbial biofilm formation in the oral cavity, methods for raising and / or maintaining plaque pH after sugar loading to a level of at least pH 5.5, methods for reducing plaque accumulation, and / or teeth and oral cavity It is useful in a method for cleaning.

  Finally, by increasing oral pH and deterring pathogenic bacteria, the compositions of the present invention are useful for promoting healing of oral ulcers or cuts.

  The compositions and methods according to the present invention can be incorporated into oral compositions for oral and dental care such as toothpastes, transparent pastes, gels, mouthwashes, sprays and chewing gums.

  Since oral tissue can be a gateway to systemic infection, enhancing oral health also benefits systemic health. Good oral health is associated with general health, including cardiovascular health. The compositions and methods of the present invention are particularly advantageous because basic amino acids, particularly arginine, is a nitrogen source that supplies the NO synthesis pathway and thus enhances microcirculation in oral tissues. Forming a less acidic oral environment also reduces gastrointestinal disturbances and creates an unfavorable environment for Helicobacter associated with gastric ulcers. In particular, arginine is required for high expression of certain immune cell receptors, such as T cell receptors, and thus arginine can enhance an effective immune response. Accordingly, the compositions and methods of the present invention are useful for enhancing systemic health, including cardiovascular health.

  As used throughout, ranges are used as shorthand for describing any value within the range. Any numerical value within that range can be selected as the end of the range. Moreover, all references cited herein are hereby incorporated by reference in their entirety. In the event of a conflict in a definition in the present disclosure and that of a cited reference, the present disclosure controls. When describing a formulation, as is commonly done in the industry, when manufactured, stored and used, these components are described by ingredients even though they may react with each other in the actual formulation. It is understood that such products can be covered by the described formulations.

  The following examples further describe and explain exemplary embodiments within the scope of the present invention. The examples are given for illustration only and are not intended to limit the invention, as many modifications are possible without departing from the spirit and scope of the invention. In addition to those shown and described herein, various modifications of the present invention will be apparent to those skilled in the art and are intended to be within the scope of the appended claims.

Oral Cleanser The formulation of the present invention is prepared with the following ingredients.

  In order to optimize the preservative system, the preservatives benzyl alcohol and methylisothiazolinone (MIT) are replaced with different preservatives in the above formulation, for antimicrobial effects, flavor effects and aesthetic effects The characteristics of the formulation were tested.

The antimicrobial preservative effect test is used to measure the antimicrobial preservative effect of a water based product formulation by a double load test. Products are developed to withstand microbial attacks introduced by normal consumer use. The test is performed on samples over time (13 weeks, 40 ° C.). The test uses two microbial populations, bacteria / yeast and mold. The product is loaded at a level of 1% on day 0 and day 7. Inoculum reduction is monitored over 28 days. The following are acceptance criteria for mouthwash formulations.
-Bacteria and yeast should be measured by plate count on day 7 after each inoculation and show a 99.9% reduction (3 log) of inoculated bacteria. There is no increase on day 7 after the second inoculation and the rest of the study is within the normal range of variation of the data.
Mold should be measured by plate count on day 14 after the second inoculation (day 21) and show a 90.0% reduction (1 log) in the inoculated mold. There is no increase from day 14 to day 21 of the second inoculation of the study and is within the normal fluctuation range of the data.

  The flavor is evaluated by a sensory stimulus evaluation by a trained perfumer.

  Aesthetics are assessed by visual comparison with a control sample having the same type and level of colorants and flavors.

  The results of the comparative test are as follows, where “re” indicates that the standard is met and “x” indicates that the standard is not met.

  These results indicate that various preservative systems behave unexpectedly in mouthwash formulations. The only preservatives that have provided acceptable microbial control are benzyl alcohol, methylisothiazolinone (MIT) and phenoxyethanol, either individually or in combination. Phenoxyethanol has an adverse effect on flavor, which can be largely masked by optimizing flavoring, but benzyl alcohol and methylisothiazolinone (MIT) are preferred.

Claims (11)

a. An effective amount of free or salt basic amino acids,
b. An oral cleanser comprising an effective amount of an aqueous solution of a preservative selected from methylisothiazolinone (MIT), benzyl alcohol, phenoxyethanol and combinations thereof.   The oral cleanser according to claim 1, wherein the basic amino acid is arginine or a salt thereof.   The oral cleanser according to any of the preceding claims, wherein the basic amino acid is present in an amount corresponding to 0.01 to 2% by weight of the total composition weight, and the weight of the basic amino acid is calculated as the free base form. . Preservatives, individually or in combination, as follows:
a. MIT: 0.0005 to 0.03% by weight
b. Benzyl alcohol: 0.05 to 0.25% by weight
c. Phenoxyethanol: 0.1 to 0.7% by weight
The mouth rinse according to any of the preceding claims, present in an amount of.   The mouthwash according to any one of the preceding claims, further comprising pyrophosphate.   The oral cleanser according to any one of the preceding claims, further comprising a synthetic anionic polymeric polycarboxylate.   The mouth rinse according to any one of the preceding claims, further comprising a fluoride ion source.   The oral cleaner according to any one of the preceding claims, wherein the oral cleaner does not contain ethanol.   The mouth rinse according to any one of the preceding claims, further comprising one or more of a wetting agent, a flavoring agent and a surfactant.   An oral cleanser according to any preceding claim, wherein the preservative comprises an amount effective to provide microbial control. A method for improving oral health, in the oral cavity of a subject in need thereof,
a. Reducing or inhibiting the formation of phagocytosis,
b. Reduction, repair or inhibition of early enamel lesions,
c. Reducing or inhibiting tooth demineralization and promoting tooth remineralization,
d. Reduction of tooth sensitivity,
e. Reduction or inhibition of gingivitis,
f. Promoting healing of ulcers or cuts in the mouth,
g. Reduced levels of acidogenic bacteria,
h. Increased relative levels of arginine degrading bacteria,
i. Inhibition of microbial biofilm formation in the oral cavity,
j. Raising and / or maintaining plaque pH after sugar loading to a level of at least pH 5.5;
k. Reducing plaque accumulation,
l. Treatment, relief or reduction of dry mouth,
m. Teeth whitening,
n. Enhancing systemic health, including cardiovascular health,
o. Reducing tooth erosion,
p. Dental immunity against cariogenic bacteria and their effects, and / or q. A method comprising applying an effective amount of a mouthwash according to any of the preceding claims for tooth and mouth cleaning.