WO2021116873A1 - Composition de soin buccal contenant des composants d'acide aminés n-acétyle pour le traitement des caries - Google Patents

Composition de soin buccal contenant des composants d'acide aminés n-acétyle pour le traitement des caries Download PDF

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Publication number
WO2021116873A1
WO2021116873A1 PCT/IB2020/061584 IB2020061584W WO2021116873A1 WO 2021116873 A1 WO2021116873 A1 WO 2021116873A1 IB 2020061584 W IB2020061584 W IB 2020061584W WO 2021116873 A1 WO2021116873 A1 WO 2021116873A1
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Prior art keywords
amino acid
acetyl amino
acid component
component
acetyl
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PCT/IB2020/061584
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English (en)
Inventor
Ingo R. Haeberlein
Brenda Schmid
Melanie N. HAUKE
Ajmal SAFI
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3M Innovative Properties Company
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Priority to EP20821417.1A priority Critical patent/EP4072686A1/fr
Publication of WO2021116873A1 publication Critical patent/WO2021116873A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A61K8/447—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof containing sulfur
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
    • A61K8/492—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid having condensed rings, e.g. indol

Definitions

  • the invention relates to an oral care composition containing certain N-acetyl amino acid components.
  • the oral care compositions and in particular the N-acetyl amino acid components contained therein were found to be effective for treating caries or reducing the risk of getting caries lesions by reducing the lactic acid release of lactic acid producing bacteria in an oral biofdm in the mouth of a living human being or animal.
  • Dental plaque which may include bacteria such as Streptococcus mutans, comprises a biofdm that forms on surfaces in the oral cavity. Dental plaque is at least partly responsible for dental caries, gingivitis, and periodontal diseases.
  • Dental plaque Bacteria in dental plaque metabolize carbohydrates (for example, simple sugars) in the mouth and produce organic acids that can etch tooth enamel, dentin, and cement. Dental plaque can serve as a substrate for the deposition of tartar or calculus. Build-up of dental plaque and calculus can lead to gingivitis and, ultimately, to periodontal disease.
  • carbohydrates for example, simple sugars
  • a currently available method to remove dental plaque from teeth is mechanical removal with, for example, dental floss or a toothbrush.
  • a toothbrush can aid in removing dental plaque from exposed surfaces of a tooth, and dental floss can aid in removing dental plaque from, for example, interproximal and subgingival surfaces.
  • Proper and regular use of dental floss and a toothbrush can mechanically remove or reduce dental plaque, and can reduce the incidence of dental caries, gingivitis, and periodontal disease.
  • Certain antimicrobial formulations are available (in the form of mouthwashes, rinses, and toothpastes, for example) to aid in the control and treatment of dental plaque, dental caries, gingivitis, and periodontal disease.
  • dental caries results from an imbalance of the metabolic activity in the individual dental biofilm. This reflects the daily clinical experiences that only a small fraction of dental plaque might end up in tooth demineralization. Even more, certain studies with dental biofilm revealed that the bacterial composition of dental plaque does not necessarily indicate the prevailing metabolic (caries) activity of the individual dental plaque. Attempts to influence the formation of biofilm and/or prevent the formation of plaque are described in various documents.
  • US 2019/0076351 Al (Stetter et al.) describes a prebiotic oral care composition containing certain dipeptides.
  • the composition is for use in selectively promoting in an oral cavity growth, metabolic activity or colonization of bacteria that have beneficial effects on oral health.
  • WO 2009/100263 A2 (Colgate-Palmolive) relates to an oral care composition comprising an effective amount of a basic amino acid, in particular arginine in free or salt form, and an effective amount of a soluble calcium salt selected glycerophosphate and salts of soluble carboxylic acids.
  • WO 2017/000837 Al (Colgate-Palmolive) relates to an oral care composition comprising arginine or lysine or salts thereof, zinc oxide and zinc citrate, and a fluoride source.
  • WO 2011/085326 Al (Harvard College) describes a method of treating, reducing or inhibiting biofdm formation by bacteria, the method comprising contacting a surface with a composition comprising an effective amount of a D-amino acid selected from D-tyrosine, D-leucine, D-methionine, D-tryptophan, or a combination thereof.
  • the composition comprises D-tyrosine, D-phenylalanine, D-proline, or a combination thereof.
  • the composition comprises two or more of D-tyrosine, D-leucine, D-phenylalanine, D-methionine, D-proline, and D-tryptophan, wherein the composition is essentially free of detergent and/or U amino acids.
  • US 5,286,480 (Boggs et al.) describes a method for reducing dental plaque coating on teeth by contacting tooth surfaces within the oral cavity for 10 sec to 30 min with a composition comprising a safe and effective amount of a complex of metal ions with N-acetylated amino acids. It is outlined that the N- acetylated amino acid component is more weakly complexed to the metal ion and is displaced by a phosphate group attached to the hydroxyapatite surface of the teeth resulting in a metal phosphate coating on the surface. A hydrous gel layer is formed which inhibits the adhesion of bacteria.
  • AU 5678773 (Jaroslav) describes an aqueous mouth wash solution having the ability to remove dental plaque and caries.
  • the composition comprises an oxidizing agent and a nitrogen containing compound such as an amino acid.
  • the solution may have a pH value of 8 to 12.
  • US 2004/028623 Al describes formulations for the removal of dental plaque, tartar and dental stains.
  • the formulations contain a substance selected from glutathione, sodium mercapto ethansulfonate, dethyldithiocarbamate, sodium thiosulfate, N-acetylcystein, cytochrome P450 and cysteamine.
  • EP 0465 921 A1 (Iscofar) relates to a chewing gum composition for the prevention and treatment of dental plaque, wherein the chewing gum composition contains a therapeutically effective amount of N- acetylcysteine.
  • US 6,228,347 B1 (Hersch) relates to a gel or paste composition for oral application to human gum to reduce symptoms of gum disease, said composition comprising a gel or paste-based carrier and an effective amount of reduced glutathione and a source of selenium to reduce said symptoms of gum disease.
  • the composition may further contain N-acetyl cysteine.
  • fluoride compounds As anticaries compounds the addition of fluoride compounds is suggested.
  • US 2014/127144 Al relates to a method of modifying the taste or flavor of a consumable product comprising adding a compound such as N-acetyl-DU-glutamic acid, N-acetyl-U- isoleucine, N-acetyl -DU-valine, N-acetyl -U-tyrosine.
  • US 5,922,346 (Hersh) relates to an antioxidant preparation, in particular to a gum for reducing free radical damage induced by tobacco products and environmental pollutants comprising as active ingredients reduced gluthathione and a selenium source. It is outlined that the addition of xylitol may reduce the susceptibility to dental caries and the use of fluorides may increase the resistance of the enamel and dentine.
  • WO 2019/214965 Al (Unilever) relates to a method of repairing oxidatively treated hair by using a treatment composition comprising 0.1 to 6 wt.% of an N-acetyl amino acid.
  • a biofdm matrix such as dental plaque may contribute to the isolation of bacteria from the protective effect of antimicrobial compounds and, thus, may interfere with the function of antimicrobial formulations such as mouthwashes, rinses, and toothpastes.
  • Such components should be easy in administering and simple in use.
  • the components should be easy to obtain or prepare and reasonable in price of manufacturing or purchase. Further, the components should not have undesired side effects like bad taste or being astringent and be sufficiently storage stable.
  • the components of the respective composition should in particular be active if used and/or applied in a permanent treatment.
  • the present invention features an oral care composition for treating caries or reducing the risk of getting caries, the oral care composition comprising a N-acetyl amino acid component contained in a solvent and/or carrier, the N-acetyl amino acid being selected from the acetyl components of alanine, cysteine, glutamic acid, glycine, leucine, proline, tyrosine, iso-leucine, tryptophan, phenylalanine and mixtures thereof, in particular the L amino acids thereof.
  • the invention is also related to a kit of parts comprising the oral care composition as described in the present text and claims and an application device.
  • Described is also a method of using the N-acetyl amino acid component or the kit of parts as described in the present text and claims for the production of an oral care composition.
  • a further aspect of the invention is directed to the use of the N-acetyl amino acid component in a method for treating caries or reducing the risk of caries, the method comprising the step of bringing the N-acetyl amino acid component in contact with an oral biofdm and/or hard dental tissue in the mouth of a living human being or animal as described in the present text and claims.
  • the treatment is particular effective if the oral care composition is applied to marginal regions of the hard dental tissue.
  • marginal regions of hard dental tissue are interproximal areas of teeth, e.g. the area between two neighbouring teeth, fissures being present on the surface of a tooth, marginal gap between a dental restoration (e.g. dental filling or dental crown) and the tooth substance.
  • a dental restoration e.g. dental filling or dental crown
  • composition is understood to be a mixture of two or more components.
  • a “dental or oral care composition” is a composition which is to be used in the dental field including the orthodontic area.
  • the composition should be not detrimental to the patient's health and thus free of hazardous and toxic components being able to migrate out of the composition.
  • Commercially available dental products have to fulfil certain requirements such as those given in DIN EN ISO 1942:2011-03.
  • a "dental surface” or “hard dental tissue” refers to tooth structures (e.g., enamel, dentin, and cementum) and bone.
  • a “tooth structure” is any tooth structure, prepared or ready for preparation by the dentist. It can be a single tooth or two or more teeth.
  • a tooth structure is also referred to as hard dental tissue in contrast to soft dental tissue (e.g. gingival).
  • “Caries” is understood as tooth decay, also known as dental caries which is a demineralization and/or breakdown of teeth due to acids produced by bacteria.
  • Distal plaque is understood as is a biofilm or mass of bacteria that grows on surfaces within the mouth.
  • biofilm refers to a matrix containing bacteria.
  • a biofilm in an oral cavity can include bacteria, epithelial cells, leukocytes, macrophages and further oral exudate.
  • a “paste” is a substance that behaves as a solid until a sufficiently large load or stress is applied, at which point it flows like a fluid.
  • Pastes typically consist of a suspension of granular material in a background fluid. The individual grains are jammed together like sand on a beach, forming a disordered, glassy or amorphous structure, and giving pastes their solid-like character. Pastes can be classified by their viscosity or their consistency comparable to dental impression material.
  • a “film forming component” is a substance which will cause a composition containing it to change from a liquid stage to a solid stage in such a manner as to form a film or coating on a surface.
  • a definition of the term “film former” can also be found in DIN 55945 (1999-07-00).
  • the term “film former” is often used in varnishes.
  • a “film” is a thin sheet or strip of a preferably flexible material. A coating of a surface with a material typically results in a film.
  • a “toothpaste” (dentifrice) is a cleaning agent for the daily individual care. It is typically used as a prophylactic measure against caries, gingivitis or periodontitis.
  • a “prophylaxis paste” is a product which is used by a profession such as a dentist or a dental hygienist to remove adherent deposits such as stain, plaque or tartar which may stick to the surface of a natural tooth, artificial tooth crown or bridge or filling material.
  • a prophylaxis paste is therefore typically used on slowly rotating paste carrier (sometimes also referred to as prophy cups). Most of the commercially available prophylaxis pastes have a different viscosity compared to toothpastes.
  • a “gel” is typically a colloidal system in which a porous matrix of interconnected particles spans the volume of a liquid medium.
  • gels are apparently solid, jelly-like materials. Both by weight and volume, gels are mostly liquid in composition and thus exhibit densities similar to liquids, however, have the structural coherence of a solid.
  • An example of a common gel is edible gelatine. Many gels display thixotropy, that is, they become fluid when agitated, but re-solidify when resting.
  • a “solvent” means a liquid which is able to at least partially disperse or dissolve a component at ambient conditions (e.g. 23°C).
  • a solvent typically has a viscosity below 5 or below 1 or below 0.1 Pa*s at 23°C.
  • a “particle” means a substance being a solid having a shape which can be geometrically determined. Particles can typically be analysed with respect to e.g. grain size. The mean particle size of a powder can be obtained from the cumulative curve of the grain size distribution and is defined as the arithmetic average of the measured grain sizes of a certain powder mixture. Respective measurements can be done using commercially available granulometers (e.g. CILAS Laser Diffraction Particle Size Analysis Instrument).
  • Ambient conditions mean the conditions which the inventive solution or composition is usually subjected to during storage and handling.
  • Ambient conditions may, for example, be a pressure of 900 to 1100 mbar, a temperature of 10 to 40 °C and a relative humidity of 10 to 100 %. In the laboratory ambient conditions are adjusted to 20 to 25 °C and 1,000 to 1,025 mbar (at maritime level).
  • a composition is “essentially or substantially free of’ a certain component, if the composition does not contain said component as an essential feature. Thus, said component is not wilfully added to the composition either as such or in combination with other components or ingredient of other components.
  • a composition being essentially free of a certain component usually does not contain that component at all. However, sometimes the presence of a small amount of the said component is not avoidable e.g. due to impurities contained in the raw materials used.
  • “And/or” means one or both.
  • the expression component A and/or component B refers to a component A alone, component B alone, or to both component A and component B.
  • additive(s) means that the term should include the singular and plural form.
  • additive(s) means one additive and more additives (e.g. 2, 3, 4, etc.).
  • N-acetyl amino acid component also includes a composition containing the N-acetyl amino acid component.
  • the composition described in the present text provides an effective means for treating caries or reducing the risk of getting caries lesions.
  • an in-vitro human saliva derived microcosm biofilm was used to apply the N-acetyl amino acid component described in the present text using different treating schemes.
  • the N-acetyl amino acid component functions as a biofdm metabolism control agent. Independent of the mechanism, the N-acetyl amino acid component is effective for treating caries or reducing the risk of getting caries lesions.
  • the oral care composition described in the present text containing a N-acetyl amino acid component as agent for treating caries or reducing the risk of getting caries is designed to move from a plaque formation inhibition composition or dental plaque removal composition or biofdm reducing composition to a composition allowing the control of the metabolic balance on dental plaque.
  • the invention shows that N-acetyl amino acid components are effective to accomplish caries activity control in a dental biofdm, i.e. being able to influence the metabolic balance of the dental biofdm.
  • the N-acetyl amino acid component proposed in the present text is easily available at reasonable costs and not harmful to the patient.
  • the respective amino acids are often better soluble in water. Aside from that, the storage stability can also be improved.
  • the N-acetyl amino acid component contained in the oral care composition described in the present text is in particular provided for use in a method or therapy of treating caries or reducing the risk of caries by reducing the lactic acid release of lactic acid producing bacteria in an oral biofdm of a human or animal being.
  • Comprised are also the orally and/or medically acceptable salts and hydrates thereof.
  • Orally and/or medically acceptable salts include the Li, Na, K and ammonium salts (such as NFLU). As the solubility of amino acid components in water is sometimes not fully satisfying, for oral care compositions better soluble amino acid components are desired.
  • solubility of the amino acids can sometimes be improved by introducing an acetyl group which blocks the free amino group, which otherwise is typically protonated by the carboxyl acid group of the amino acid forming a zwitter ionic structure.
  • the N-acetyl amino acid which are suitable for treating caries or reducing the risk of caries are selected from the acetyl components of alanine, valine, cysteine, glutamic acid, glycine, leucine, proline, tyrosine, iso-leucine, tryptophan, phenylalanine and mixtures thereof, wherein the L form of the amino acid is preferred.
  • N-acetyl amino acids selected e.g. from the acetyl components of arginine, asparagine, aspartic acid, histidine, serine and threonine were found to be not sufficiently effective for treating caries or reducing the risk of getting caries.
  • the N-acetyl amino acid component is typically present in the oral care composition in an amount being effective for reducing the lactic acid release of acetic acid releasing bacteria by at least 40 or at least 45 or at least 50% compared to a control composition not containing the N-acetyl amino acid component.
  • Range 0.1 to 10 wt.% or 0.5 to 8 wt.%; with respect to the weight of the composition.
  • the N-acetyl amino acid component is used in combination with water.
  • the oral care composition comprises one or more of the N-acetyl amino acid components and water.
  • Water is used for dissolving or dispersing the N-acetyl amino acid component, at least partially. Water is typically present in an amount sufficient to fully dissolve the N-acetyl amino acid component and other optional components being present in the oral care composition.
  • the oral care composition may comprise water in the following amounts:
  • Range 1 to 98 or 10 to 95 or 20 to 90 wt.%; wt.% with respect to the whole oral care composition.
  • the ratio of N-acetyl amino acid component to water is typically at least 0.1 / 100, or at least 0.5 / 100 with respect to weight.
  • the ratio of N-acetyl amino acid component to water can be in a range of 0.1 / 100 to 10 / 100, or in a range of 0.5 / 100 to 5 / 100 with respect to weight.
  • the N-acetyl amino acid component may also be used in combination with a carrier component.
  • the oral care composition may comprise one or more N-acetyl amino acid components, one or more carrier components and optionally water.
  • the nature and structure of the carrier component is not particularly limited, unless the desired result cannot be achieved.
  • Carrier components may help to adjust the rheological properties of the N-acetyl amino acid component containing composition to support the application and/or to trigger the release of the active agent(s) contained in the composition.
  • the carrier component is typically present in the following amount(s):
  • Suitable carrier components are gel-forming agents or paste-forming agents.
  • gel-forming or paste-forming agents include Irish moss, carboxymethyl cellulose, gum tragacanth, gum arabic, gum Karaya, sodium alginate, hydroxyethyl cellulose, methyl and ethyl cellulose, carrageenan, xanthan gum, polyvinyl pyrrolidone, and mixtures thereof.
  • the carrier component is a film-forming agent.
  • Film-forming agents are suitable to improve adherence of the quaternary ammonium alkyl component(s) contained in the composition described in the present text to hard dental tissue, such as a tooth surface.
  • film-forming agent(s) are present, the components contained in the composition described in the present text are typically dissolved or dispersed in the film forming component(s) and form together with the film forming component(s) a film or coating on the surface of hard dental tissue.
  • the molecular weight (Mw) of the film -forming agent can vary over a wide range (e.g. 2,000 to 1,200,000 g/mol). Typical ranges include 10,000 to 500,000 or 20,000 to 300,000 g/mol.
  • the molecular weight is typically provided by the manufacturer of the respective film-forming component. If desired, the molecular weight can be determined by GPC technology, using e.g. a polystyrene standard.
  • the film forming component might not be able to form a sufficiently durable film or coating. Thus, the effect of a delayed release of the N- acetyl amino acid component might not be obtained.
  • the film caused or produced by the film-forming agent typically has a thickness in a range of 0.5 pm to 100 pm or 10 pm to 50 pm.
  • Film formers or film-forming agents can be classified as natural film former, semi-synthetic film formers, cellulose derivatives, poly(meth)acrylates and vinyl polymers.
  • natural film-forming agents include shellac, mastix, sandarac, tolubalsam, dammar resin, benzoe resin, keratin, maizin, gum Arabic and gelatines.
  • semi -synthetic film-forming agents examples include gelatines treated with formaldehyde and salol (acetaldehyde phenol condensate).
  • Typical cellulose derivatives include cellulose acetate phthalate, hydroxyethylcellulose, hydroxy- propylcellulose, methylcellulose, ethylcellulose and hydroxypropylmethyl cellulose phthalate.
  • poly(meth)acrylates examples include copolymers of (meth)acrylic esters and amino functional (meth)acrylates, copolymers of (meth)acrylic acid and methyl methacrylate, polyacrylamide, polyacrylic acid and salts thereof, in particular partial salts thereof, including sodium salts.
  • vinyl polymers include polyvinyl pyrrolidone, polyvinyl acetate phthalate (e.g. hydroxypropyl- and hydroxypropyl-methylcellulose), homo- and copolymers of poly vinylacetate, homo- and copolymers of polyvinylpropionate, styrene acrylics, ethylene vinyl acetate, poly(hydroxyethyl methacrylate, poly(vinylethylene glycol acrylate, polyvinyl alcohol(s).
  • polyvinyl pyrrolidone polyvinyl acetate phthalate (e.g. hydroxypropyl- and hydroxypropyl-methylcellulose), homo- and copolymers of poly vinylacetate, homo- and copolymers of polyvinylpropionate, styrene acrylics, ethylene vinyl acetate, poly(hydroxyethyl methacrylate, poly(vinylethylene glycol acrylate, polyvinyl alcohol(s).
  • film -forming agent(s) include (e.g. fully or partially hydrolyzed) polyvinylalcohol, polymethylvinylether, polyvinylpyrrolidone, (e.g. aqueous) acrylic resin dispersions (e.g. EudragitTM, commercially available from Rohm), gelatine, polysaccharides (e.g. agarose), polyacrylamide, copolymers of vinylpyrrolidinone and acrylamide, hydrophilic cellulose derivatives (e.g.
  • hydroxyethylcellulose hydroxypropylcellulose, methylcellulose
  • homo- and copolymers of polyvinylacetate homo- and copolymers of polyvinylpropionate, styrene acrylics, ethylene vinyl acetate, polyurethanes, hydroxylated acrylates such as poly(hydroxyethyl methacrylate), poly(vinylethylene glycol acrylate), and combinations and mixtures thereof.
  • film-forming agents which are sometimes preferred include polyvinyl alcohol, gelatine, polyacrylic acid, partially neutralized polyacrylic acid and mixtures thereof.
  • a film-forming agent is present, it is typically present in the following amounts:
  • the N-acetyl amino acid component is used in combination with abrasive particles.
  • the oral care composition may comprise one or more N-acetyl amino acid components, abrasive particles and optionally carrier component(s) and water.
  • abrasive particles examples include perlite, bentonite, silica, alumina, aluminium hydroxide, ilmenite (FeTiCfi), zircon oxide, zircon silicate, calcium carbonate, sodium bicarbonate, titanium dioxide , precipitated lime, chalk, flour of pumice, zeolites, talcum, kaolin, kieselguhr, aluminium oxide, silicates and mixtures thereof.
  • the N-acetyl amino acid component is used in combination with certain free, i.e. non acetylated amino acids.
  • the oral care composition comprises one or more N-acetyl amino acid components, one or more amino acids, water, optionally carrier component(s) and optionally abrasive particles.
  • the amino component(s) are used for modifying the structure of the oral biofilm and thus have an influence on the overall environment where the lactic acid producing bacteria are located.
  • the amino acid(s) may have a direct impact on the metabolism of the lactic acid releasing bacteria.
  • amino acids were found to be useful for achieving the desired results: glycine, leucine, isoleucine, lysine, methionine, phenylalanine, serine, threonine, valine, tryptophan and mixtures thereof, with the following amino acids being sometimes preferred: glycine, phenylalanine, serine, isoleucine, leucine, methionine, with glycine and phenylalanine being sometimes being even more preferred.
  • the amino acids may be natural or synthetic.
  • amino acids might be in D- or L-configuration, wherein the L-configuration is preferred.
  • the N-acetyl amino acid component containing oral care composition described in the present text does typically not contain these amino acids in an effective amount, e.g. more than 0.5 or more than 0.3 or more than 0.1 wt.%.
  • the amino acids selected from glycine, leucine, isoleucine, methionine, phenylalanine, serine, threonine, valine, tryptophan and mixtures thereof are present in an amount sufficient for achieving the desired result. If present, the amino acids contained in the N-acetyl amino acid component containing oral care composition are used in a therapeutically effective amount being sufficient to influence the lactic acid release metabolism of lactic acid releasing bacteria in an oral biofilm.
  • the N-acetyl amino acid component containing oral care composition and the amino acids contained therein are used for a time period being sufficient to influence the lactic acid release metabolism of lactic acid releasing bacteria in an oral biofilm.
  • N-acetyl amino acid component containing oral care composition and the amino acids contained therein are typically present in an amount and applied for a time period effective to reduce the lactic acid release of lactic acid producing bacteria by more than 40% or more than 45% or more than 50% compared to the situation before the oral care composition described in the present text was used.
  • amino acid(s) are typically present in the following amounts:
  • Range 0.1 to 15 or 1 to 12 or 2 to 10 wt.%; wt.% with respect to the whole oral care composition.
  • glycine in an amount of 0.1 to 10 wt.%; or leucine in an amount of 0.1 to 5 wt.%; or isoleucine in an amount of 0.1 to 5 wt.%; or methionine in an amount of 0.1 to 10 wt.%; or phenylalanine in an amount of 0.1 to 5 wt.%; or serine in an amount of 0.1 to 10 wt.%; or threonine in an amount of 0.1 to 10 wt.%; or valine in an amount of 0.1 to 8 wt.%; or tryptophan in an amount of 0.1 to 2 wt.%; wt.% with respect to the whole oral care composition.
  • glycine in an amount of 1 to 10 wt.%; or leucine in an amount of 1 to 5 wt.%; or isoleucine in an amount of 2 to 5 wt.%; or methionine in an amount of 2 to 10 wt.%; or phenylalanine in an amount of 1 to 5 wt.%; or serine in an amount of 1 to 10 wt.%; or threonine in an amount of 6 to 10 wt.%; or valine in an amount of 3 to 8 wt.%; or tryptophan in an amount of 0.5 to 2 wt.%; wt.% with respect to the whole oral care composition.
  • the ratio of amino acid(s) to water is typically at least 0.1 / 100, or at least 1.5 / 100, or at least 2 / 100 with respect to weight.
  • the ratio of amino acid(s) to water can be in a range of 0.1 / 100 to 15 / 100, or in a range of 1.5 / 100 to 12 / 100, or in a range of 2 / 100 to 10 / 100 with respect to weight.
  • the ratio of N-acetyl amino acid component to amino acid(s) can be in a range of 1 / 100 to 100 / 1, or in a range of 1 / 10 to 10 / 1, or in a range of 1 / 5 to 5 / 1 with respect to weight.
  • the N-acetyl amino acid component is used in combination with an ammonium alkyl sulfonate or carbonate component.
  • the invention is also related to an oral care composition
  • an oral care composition comprising one or more N-acetyl amino acid components, one or more ammonium alkyl sulfonate or carbonate components, water, optionally carrier component(s) and optionally abrasive particles.
  • ammonium alkyl sulfonate or carbonate component there is no need for an ammonium alkyl sulfonate or carbonate component to be present, however, the presence of an ammonium alkyl sulfonate or carbonate component in combination with the N-acetyl amino acid component may further help or even improve the efficacy or capacity of the oral care composition described in the present text.
  • Suitable ammonium alkyl sulfonate or carbonate component may be characterized by either of the following formulas (I), (II) or (III):
  • ammonium alkyl sulfonate or carbonate component examples include 3-(N,N-Dimethyloctyl- ammonio) -propane -sulfonate, 3-(Decyldimethylammonio)-propane-sulfonate, 3-(Dodecyldimethyl- ammonio) -propane -sulfonate, 3-(4-Heptyl)phenyl-3-hydroxypropyl)dimethylammonio-propane- sulfonate, Amidosulfobetaine-14, Cocamidopropylbetain, and mixtures thereof.
  • N-acetyl amino acid component is typically used in excess.
  • a ratio of N-acetyl amino acid component to ammonium alkyl sulfonate or carbonate component in the range of 50 : 1 to 1.5 : 1 or 30 : 1 to 1.5 : 1 with respect to weight was found to be particularly useful.
  • the N-acetyl amino acid component may function as a biofdm metabolism control agent, whereas the ammonium alkyl sulfonate or carbonate component may function as an agent for modifying the structure of the biofdm or as a kind of cell membrane modifying agent.
  • N-acetyl amino acid component is selected from N-acetyl proline, N- acetyl-phenyl alanine or mixtures thereof and wherein the ammonium alkyl sulfonate or carbonate component is selected from 3-(N,N-Dimethyloctylammonio)-propane-sulfonate, 3-(Decyldimethyl- ammonio) -propane -sulfonate, 3-(Dodecyldimethylammonio)-propane-sulfonate, 3-(4-Heptyl)phenyl-3- hydroxypropyl)dimethylammonio-propane-sulfonate, Amidosulfobetaine-14, Cocamidopropylbetain, and mixtures thereof, in particular Amindosulfobetain-14.
  • ammonium alkyl sulfonate or carbonate component for use in a method of treating caries or reducing the risk of caries is described in PCT/IB2020/058877 (3M IPC). The content of this reference is herewith incorporated by reference.
  • the presence of a synergistic effect can be shown by comparing the lactic acid release of a biofdm which has not been treated with a lactic acid reducing composition (control; lactic acid release value set as 100%) with the lactic acid release of a biofdm having been treated by either of the following: a) a composition comprising N-acetyl amino acids, b) a composition comprising ammonium alkyl sulfonate or carbonate component, and c) a composition comprising N-acetyl amino acids and ammonium alkyl sulfonate or carbonate components.
  • the synergistic effect becomes in particular visible if only small amounts of these components are tested (e.g. a composition comprising N-acetyl amino acids in an amount in the range of 0.01 to 0.2 wt.% and a composition comprising ammonium alkyl sulfonate or carbonate components in an amount of 0.003 to 0.008 wt.%).
  • the N-acetyl amino acid component containing oral care composition described in the present text may also comprise additive(s).
  • One or more additives can be present, if desired.
  • additive(s) are typically present in the following amount(s):
  • Range 0.01 to 10 or 0.1 to 8 or 0.5 to 6 wt.%; wt.% with respect to the whole oral care composition.
  • Additive(s) which might be present include stabilizer(s), colourant(s), phosphate releasing agent(s), calcium releasing agent(s), anti-microbial agent(s), buffer(s), humectant(s), preservative agent(s), flavour additive(s) and mixtures thereof.
  • the composition might contain one or more stabilizer(s) as an additive.
  • the storage stability of the dental composition might be improved. That is, the individual components of the composition do not separate over time.
  • a composition is defined as storage -stable, if the components do not separate from each other within 6 months or 12 months or 24 months or 36 months at ambient conditions.
  • a stabilizer is present, it is typically, present in a low amount.
  • Amounts, found to be useful, include 0.01 to 3 wt.% or 0.1 to 1 wt.% with respect to the weight of the whole composition.
  • stabilizer(s) examples include copolymers of 2,5-furandione with 1,9-decadiene and methoxy- ethene (e.g. StabilizeTM, International Specialty Products (ISP) Comp.) and carboxy vinyl polymers (e.g. CarbopolTM, Lubrizol Advanced Materials Comp.).
  • Stabilizers typically have a mean particle size below 500 pm or below 250 pm or below 100 pm.
  • the composition comprises one or more colourants.
  • Typical ranges include 0.01 wt.% to 5 wt.% or 0.1 wt.% to 3 wt.% with respect to the whole composition.
  • a colourant may allow an easy detection in a patient's mouth (especially compared to oral tissue and/or tooth substance) and control whether after the treatment all residues of the composition have been removed.
  • a blue, green or violet colour may be suitable.
  • Colouring of the dental composition can be achieved by incorporating colorants or pigments (organic and inorganic) into the composition.
  • colourants include red iron oxide 3395, BayferroxTM 920 Z Yellow, NeazoponTM Blue 807 (copper phthalocyanine-based dye) or Helio Fast Yellow ER and mixtures thereof.
  • the composition comprises one or more phosphate releasing agent(s) as an additive. There is no need for a phosphate releasing agent to be present at all.
  • Typical ranges include 0.01 wt.% to 5 wt.% or 0.1 wt.% to 3 wt.% with respect to the whole composition.
  • phosphate and/or calcium releasing agent(s) examples include calcium pyrophosphate, calcium carbonate, dicalcium phosphate dehydrate, amorphous calcium phosphate, casein phosphopeptide, calcium sodium phosphosilicate, trimetaphosphate, and mixtures thereof.
  • composition comprises anti-microbial agent(s).
  • Typical ranges include 0.01 wt.% to 2 wt.% or 0.1 wt.% to 1 wt.% with respect to the whole composition.
  • an anti-microbial agent might help reducing health risks for professionals in the dental offices and laboratories as well as for patients.
  • Useful anti -microbial agents include chlorhexidine or derivatives thereof and aldehydes (glutaraldyde, phthalaldehyde) and chlorhexidine or its derivatives and salts of phenolics or acids. It can also be preferred to use acid adducts of chlorhexidine or its derivatives like e.g., acetates, gluconates, chlorides, nitrates, sulphates or carbonates.
  • Chlorhexidine and its derivatives are commercially available in water-based solutions (e.g. a 20 % aqueous solution of CHX digluconate, CAS 18472-51-0) or as a pure compound or as a salt.
  • water-based solutions e.g. a 20 % aqueous solution of CHX digluconate, CAS 18472-51-0
  • pure Chlorohexidine compound CAS 55-56-1
  • CHX salts like CHX diacetate monohydrate (CAS 56-95-1) or CHX dihydrochloride (CAS 3697-42-5) are preferred.
  • CHX also seems to be especially suited as an additive due in part to its well-known and proven anti-microbial action against Gram-positive and Gram-negative microorganisms including the oral Streptococci and Lactobacilli.
  • CHX is bacteriostatic for Mycobaterium.
  • CHX is also active against yeasts including Candida albicans and viruses including HIV, HBV, HCV, Influenza- and Herpes virus.
  • a further advantage of CHX is its low toxicity.
  • Preferred anti-microbial agents include hexitidin, cetypyridiniumcloride (CPC), chlorhexidin (CHX), triclosan, stannous chloride, benzalkonium chloride, non-ionic or ionic surfactants (e.g. quaternary ammonium compounds), alcohols [monomeric, polymeric, mono-alcohols, poly-alcohols (e. g. xylitol, sorbitol), aromatic (e. g. phenol)], antimicrobial peptides (e. g. histatins), bactericins (e. g. nisin), antibiotics (e. g. tetracycline), aldehydes (e.
  • inorganic and organic acids e. g. benzoic acid, salicylic acid, fatty acids
  • derivative of such acids such as esters (e. g. p-hydroxy benzoate or other parabenes, laurizcidin), enzymes (e. g. lysozyme, oxidases), proteins (e. g. enamel matrix protein, proline rich proteins), fluoride, EDTA, essential oils (e. g. thymol).
  • composition can comprise one or more buffer(s) as an additive.
  • a buffer there is no need for a buffer to be present at all. However, if it is present, it is typically present in an amount of at most 5 wt.% or of at most 3 wt.% or of at most 2 wt.% with respect to the whole composition. Typical ranges include 0.1 wt.% to 5 wt.% or 1 wt.% to 3 wt.% with respect to the whole composition.
  • buffers examples include acetic acid/acetate, tris(hydroxymethyl)amino- methane (TRIS), N-(2-acetamido)-2-aminoethane sulfonic acid (ACES), N-(2-acetamido)immino- diacetate (ADA), N,N-bis(2-hydroxyethyl)-2-aminoethane sulfonic acid (BES), 2,2-bis-(hydroxyethyl)- iminotris(hydroxylmethyl)methane (BIS-TRIS), 2-(cyclohexylamino)ethane sulfonic acid (CHES), 2-[4- (2-hydroxyethyl-l-piperazine)]ethane sulfonic acid (HEPES), 3-[4-(2-hydroxyethyl-l- piperazinyl)] propane sulfonic acid (HEPPS), 2-morpholinoethane sulfonic acid (MES), 3-
  • composition might contain one or more humectant(s) as an additive.
  • Typical ranges include 0.01 wt.% to 5 wt.% or 0.1 wt.% to 3 wt.% with respect to the whole composition.
  • humectant(s) examples include glycerine, sorbitol, mannitol, xylitol, propylene glycol, polyethylene glycol and mixtures thereof.
  • preservative agent(s) examples include sodium benzoate, citric acid and its salts, and combinations thereof.
  • flavour additive(s) examples include peppermint, spearmint, and combinations thereof.
  • the oral care composition comprises or essentially consists of or consists of:
  • Component A N-acetyl amino acid in an amount of 0.1 to 10 wt.%;
  • Component B (water) in an amount of 5 to 98 wt.%;
  • Component C (carrier component) in an amount of 0 to 90 wt.%
  • Component D (amino acid) in an amount of 0 to 15 wt.%
  • Component E additive in an amount of 0 to 10 wt.%; wt.% with respect to the whole composition.
  • the oral care composition comprises or essentially consists of or consists of:
  • Component A N-acetyl amino acid in an amount of 0.1 to 10 wt.%;
  • Component B (water) in an amount of 5 to 98 wt.%;
  • Component C (carrier component) in an amount of 1 to 90 wt.%;
  • Component D amino acid in an amount of 0 to 15 wt.%
  • Component E additive in an amount of 0 to 10 wt.%; wt.% with respect to the whole composition.
  • the oral care composition comprises or essentially consists of or consists of:
  • Component A N-acetyl amino acid in an amount of 0.1 to 10 wt.%;
  • Component B (water) in an amount of 5 to 98 wt.%;
  • Component C (carrier component) in an amount of 1 to 90 wt.%;
  • Component D (amino acid) in an amount of 0.1 to 15 wt.%;
  • Component E additive in an amount of 0 to 10 wt.%; wt.% with respect to the whole composition.
  • the composition typically has a pH value in the range of 6 to 8. Thus, the composition is essentially neutral.
  • the composition can also be characterized by its viscosity. Depending on its chemical formulation, the viscosity may vary over a huge range.
  • the viscosity is typically in a range of 1 to 10 mPa*s or 1 to 1,000 mPa*s at 23°C.
  • the viscosity is typically in a range of 2,000 to 200,000 mPa*s at 23°C.
  • the viscosity of liquids can be measured using a Physica MCR 301 Rheometer (Anton Paar, Graz, Austria) with a cone/plate geometry CP25-1 under controlled shear rate at 23 °C (e.g. 100 s 1 ). The diameter is 25 mm, the cone angle 1°, and the separation between the cone tip and the plate 49 pm.
  • the viscosity of pastes can be determined using a Physica MCR 301 Rheometer (Anton Paar, Graz, Austria) with a plate/plate geometry (PP15) at a constant shear rate of 1 s 1 in rotation at 28 °C.
  • the diameter of the plates is 10 mm and the gap between the plates is set to 2.0 mm.
  • the N-acetyl amino acid component described in the present text is particularly useful for producing an oral care composition.
  • the oral care composition containing the N-acetyl amino acid component described in the present text can typically be produced as follows:
  • the N-acetyl amino acid component is provided and mixed with the other components of the oral care composition such as water, the carrier component(s), amino acid(s) and the additive(s), if present.
  • the mixing is done by dissolving or dispersing the N-acetyl amino acid component in the carrier component(s) and additive(s), if desired, with the aid of a mixing device.
  • the mixing can also be accomplished shortly before the use of the oral care composition or the oral care composition can already be provided in a mixed and storage stable form.
  • the invention is also directed to a kit of parts for use in a method or therapy of treating or reducing the risk of getting caries.
  • the kit of parts typically comprises Part A comprising the N-acetyl amino acid component described in the present text, preferably in combination with amino acids or ammonium alkyl sulfonate or carbonate component(s) described in the present text,
  • Part B comprising water for dissolving or dispersing the N-acetyl amino acid component, optionally in combination with a carrier component, and optionally Part C comprising an application device.
  • the other components such as amino acid(s), carrier component(s) or additive(s) as described in the present text can be present in Part A or Part B or Part A and Part B, as desired.
  • Providing the components of the composition in separated parts can be beneficial to improve the storage stability.
  • the practitioner Before use, the practitioner will prepare the oral care composition by combining the respective components of the individual parts.
  • the application of the oral care composition can be done by various means and/or using various devices.
  • Possible application devices include cups, sponges, brushes, dental trays, syringes, mouth guards, and clear tray aligners.
  • Clear tray aligners can straighten a dental patient’s teeth without the need for using wires and brackets of traditional braces.
  • the aligners typically consist of a sequence of clear, removable trays that fit over the teeth to straighten them.
  • composition or kit of parts described in the present text in combination with a dental tray, mouth guard or clear tray aligner can be advantageous, as these kinds of devices are typically worn for a longer period of time (e.g. 10 min to 12 hrs) and thus are well suited for applying the oral care composition described in the present text for a longer period of time, if desired.
  • N-acetyl amino acid component containing oral care composition described in the present text in combination with a dental tray, mouth guard or clear tray aligner, providing the N-acetyl amino acid composition in the form of a paste or gel was found to be advantageous.
  • the oral care composition described in the present text is typically packaged in a suitable packaging device.
  • the size and shape of the packaging device typically depends on the form how the composition is provided.
  • Suitable packaging devices include sealable bottles, tubes, vessels or foil bags (including glass or plastic bottles, e.g. equipped with a screw cap), blisters, syringes, etc.
  • the packaging device might be designed for single-use or repeated use.
  • the N-acetyl amino acid component can be used and applied in different forms or shapes.
  • the N-acetyl amino acid component is provided in a liquid, e.g. in the form of an oral rinse or a mouth wash.
  • the composition is provided as part of a gel.
  • the composition is provided as part of a paste, e.g. in the form of a toothpaste.
  • the composition is provided as part of a gum, e.g. in the form of a chewing gum.
  • the composition is provided in a form which results in a coating after application.
  • Such an application typically contains a film forming agent.
  • N-acetyl amino acid component described in the present text can be used include prophy pastes, prophy powder, varnishes, coatings, etc.
  • the N-acetyl amino acid component has to be brought in contact with the oral biofilm or hard dental tissue.
  • the oral biofilm is typically located on tooth surfaces, in particular hard dental tissue.
  • the bringing into contact can be achieved by different means, including rinsing, spraying, brushing, swabbing, coating or combinations thereof.
  • the bringing into contact is typically done for a time period being sufficient for causing the desired effect.
  • the bringing into contact is typically done for a duration of at least 1 min or of at least 2 min or at least 3 min or at least 4 min.
  • the step of bringing into contact can be repeated several times.
  • the oral care composition is applied in periodic application scheme.
  • Possible daily repeating schemes for a periodic application scheme are: at least 2-times for 1 to 5 min within 24 hours; at least 3-times for 1 to 5 min within 24 hours.
  • N-acetyl amino acid component is provided in the form of a mouth wash or toothpaste.
  • the oral care composition is applied in a continuous application scheme.
  • Possible daily repeating schemes for a continuous application scheme are: at least 1 hour within 24 hours; at least 5 hours within 24 hours.
  • N-acetyl amino acid component is provided in the form of a gel or varnish to be applied either directly on the surface of the tooth structure or with the help of an application device.
  • the N-acetyl amino acid component described in the present text is applied to form a coating or film which can persist on a tooth surface for at least 1, 2, 3 or 5 or 10 days up to 12 months or even longer.
  • the N-acetyl amino acid component is applied together with film -forming agent(s).
  • the N-acetyl amino acid component containing oral care composition described in the present text does typically not comprise the following components alone or in combination: oxidizing components in an amount of more than 0.5 wt.%; heavy metal components comprising Zn, Sn or Cu in an amount of more than 0.1 wt.%; fluoride anions in an amount of more than 0.2 or more than 0.15 or more than 0.1 wt.%; wt.% with respect to the whole composition.
  • composition described in the present text are essentially free of abrasive particles, in particular free of the abrasive particles described in the text above.
  • Essentially free means less than 1 or less than 0.5 or less than 0.1 wt.% or do not contain abrasive particles at all. Common to most of these substances is typically a comparable high hardness, e.g. above about Mohs 4 or above about 5.
  • compositions described in the present text are essentially free of oxidizing component(s) (e.g. less than 0.5 or less than 0.3 or less than 0.1 wt.%) or do not contain oxidizing components at all.
  • Oxidizing component(s) which are typically not present are peroxide, hypochlorite, perborate, persulfate, peroxyphosphate, peroxy carbonate.
  • oxidizing components have a negative effect in that they may react with the amino acids being present in the composition having the result that the reaction products are no longer suitable for acting as a metabolism modifying agent.
  • compositions described in the present text are essentially free of heavy metal component(s), in particular those comprising Zn, Sn or Cu (e.g. less than 0.1 or less than 0.05 or less than 0.01 wt.%) or do not contain heavy metal component(s) at all.
  • heavy metal components may have a negative effect, too, in that they may react with the amino acids being present in the composition (e.g. by forming insoluble complexes) having the result that the reaction products are no longer suitable for acting as a metabolism modifying agent.
  • compositions described in the present text should be sufficiently biocompatible, that is, the composition should not produce a toxic, injurious, or immunological response in living tissue.
  • the N-acetyl amino acid component described in the present text for use in a method of treating caries or reducing the risk of getting caries by reducing the lactic acid release of lactic acid producing bacteria in an oral biofilm in the mouth of a living human or animal, the N-acetyl amino acid component being applied in combination with water, the N-acetyl amino acid component being used in an amount of 0.1 to 10 wt.% with respect to the weight of the composition comprising water and the N-acetyl amino acid, the composition having a pH in the range of 6 to 8 and having a viscosity of 1 to 1,000 mPa*s at 23°C.
  • the N-acetyl amino acid as described in the present text for use in a method of treating caries or reducing the risk of getting caries by reducing the lactic acid release of lactic acid producing bacteria in an oral biofdm in the mouth of a living human or animal, the N-acetyl amino acid component being applied as oral care composition comprising water and gel-forming or paste-forming component(s), the ratio of the N-acetyl amino acid component to water being in a range of 0.1: 100 to 10: 100 with respect to weight, the oral care composition having a pH in the range of 6 to 8 and having a viscosity of 2,000 to 20,000 mPa*s at 23°C.
  • the N-acetyl amino acid component as described in the present text for use in a method of treating caries or reducing the risk of getting caries by reducing the lactic acid release of lactic acid producing bacteria in an oral biofdm in the mouth of a living human or animal, the N-acetyl amino acid component being applied as oral care composition comprising water and amino acid(s), the ratio of the N-acetyl amino acid component to water being in a range of 0.1: 100 to 10:100 with respect to weight, the amino acid(s) being selected from glycine, leucine, isoleucine, methionine, phenylalanine, serine, threonine, valine, tryptophan and mixtures thereof, the method of treating caries or reducing the risk of getting caries by reducing the lactic acid release comprising the step of applying the oral care composition to the oral biofdm for at least 1 min.
  • the N-acetyl amino acid as described in the present text for use in a method of treating caries or reducing the risk of getting caries by reducing the lactic acid release of lactic acid producing bacteria in an oral biofdm in the mouth of a living human or animal, the N-acetyl amino acid component being applied in combination with water, the ratio of the N-acetyl amino acid component to water being in a range of 0.1: 100 to 10: 100 with respect to weight, the composition having a pH in the range of 6 to 8, the method of treating caries or reducing the risk of getting caries by reducing the lactic acid release comprising the steps of applying the N-acetyl amino acid component to the oral biofilm and/or hard dental tissue according to either of the following application schemes: at least 2 times for at least 1 min within 24 hours, for at least 1 hour within 24 hours, or for at least 2 days.
  • the N-acetyl amino acid component as described in the present text for use in a method of treating caries or reducing the risk of getting caries by reducing the lactic acid release of lactic acid producing bacteria in an oral biofdm in the mouth of a living human or animal, the N-acetyl amino acid component being applied in combination with water and amino acid(s), the ratio of the N-acetyl amino acid component to water being in a range of 0.1:100 to 10:100 with respect to weight, the amino acid being selected from glycine in an amount of 0.1 to 10 wt.%; or leucine in an amount of 0.1 to 5 wt.%; or isoleucine in an amount of 0.1 to 5 wt.%; or methionine in an amount of 0.1 to 10 wt.%; or phenylalanine in an amount of 0.1 to 5 wt.%; or serine in an amount of 0.1 to 10 wt.%; or threonine in an amount of 0.1
  • the N-acetyl amino acid component as described in the present text for use in a method of treating caries or reducing the risk of getting caries by reducing the lactic acid release of lactic acid producing bacteria in an oral biofdm in the mouth of a living human or animal, the N-acetyl amino acid component being applied in combination with film-forming, gel-forming or paste-forming component(s), the N-acetyl amino acid component being applied to the oral biofdm and/or hard dental tissue for at least 2 days.
  • the N-acetyl amino acid component as described in the present text for use in a method of treating caries or reducing the risk of getting caries by reducing the lactic acid release of lactic acid producing bacteria in an oral biofdm in the mouth of a human being or animal, the N-acetyl amino acid component being used in combination with water, the ratio of the N-acetyl amino acid component to water being in a range of 0.1:100 to 10:100 with respect to weight, the method of treating caries or reducing the risk of getting caries comprising the step of bringing the N-acetyl amino acid component into contact with the oral biofdm according to either of the following application schemes: at least 2 times for at least 1 min within 24 hours, or for at least 1 hour within 24 hours, or for at least for 2 days.
  • the N-acetyl amino acid component as described in the present text for use in a method of treating caries or reducing the risk of getting caries by reducing the lactic acid release of lactic acid producing bacteria in an oral biofdm in the mouth of a living human or animal, the N-acetyl amino acid component being applied as oral care composition comprising in addition water and ammonium alkyl sulfonate or carbonate component(s).
  • ammonium alkyl sulfonate or carbonate component(s) being preferably selected from 3-(N,N- Dimethyloctylammonio)-propane-sulfonate, 3 -(Decyldimethylammonio) -propane -sulfonate, 3-(Dodecyl- dimethylammonio)-propane-sulfonate, 3-(4-Heptyl)phenyl-3-hydroxypropyl)dimethylammonio-propane- sulfonate, Amidosulfobetaine-14, Cocamidopropylbetain and mixtures thereof, the method of treating caries or reducing the risk of getting caries by reducing the lactic acid release comprising the step of applying the oral care composition to the oral biofdm for at least 1 min.
  • compositions can be used in a method or therapy described in the present text.
  • a method by determination of lactic acid and/or lactate wherein, in case of saliva having a sample volume of 0.1 ml, between 0.001 and 100 Units of lactate dehydrogenase are added and pyruvate is added in concentrations of between 0.001 pmol and 5 pmol per 0.1 ml of sample volume and, in the case of biofilms which have been obtained from an oral cavity surface of 0.01 to 25 cm 2 , between 0.001 and 100 Units of lactate dehydrogenase are added, and wherein in both cases NAD is present in a concentration between 0.001 and 10 mmol/1 based on the entire test mixture and subsequently the resulting amount of NADH is measured, wherein the resulting amount of NADH detected is used to calculate the amount of lactic acid and/or lactate in the saliva or biofdm.
  • the patient collects saliva from the mouth and transfers 0.6 ml into a reaction vessel containing 0.25 g of sucrose.
  • the reaction vessel is closed and shaken for 5 sec. After 3 min, the signal-producing solution is added.
  • the reaction vessel is shaken for 5 sec. After 3 min, 0.4 ml of acetic acid solution (1 mol/l in water) is added.
  • the course of the reaction can be followed by the colour change from yellow to blue. Yellow indicates no risk of caries, and the more intense the blue colour, the higher the lactic acid formation.
  • the signal-producing solution contains the following components: 0.1 ml of NAD solution (30 mmol/1 NAD in Glygly buffer 50 mmol/1, pH 9.0), 0.1 ml of MTT (1.5 mmol/1 MTT in Glygly buffer 50 mmol/1, pH 9.0), 0.1 ml of PMS solution (1.0 mmol/1 PMS in Glygly buffer 50 mmol/1, pH 9.0), 0.1 ml of LDH solution (lactate dehydrogenase (LDH) 60 units/ml in Glygly buffer 50 mmol/1, pH 9.0) and 0.1 ml of pyruvate solution (25 mmol/1 in Glygly buffer 50 mmol/1, pH 9.0), with MTT: 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, NAD: nicotinamide adenine dinucleotide, PMS: phenazine methosulphate;
  • the accumulation of lactic acid in the supernatant was measured by using the Lactic acid dehydrogenase (LDH)- Nicotinamide-adenine-dinucleotide (NAD)- Phenazine Methosulphate (PMS) - Thiazolyl blue tetrazolium bromide (MTT) - enzyme assay.
  • LDH Lactic acid dehydrogenase
  • NAD Nicotinamide-adenine-dinucleotide
  • PMS Phenazine Methosulphate
  • MTT Thiazolyl blue tetrazolium bromide
  • the biofdm samples were washed four times with 1.0 ml PBS solution for 30 sec each. After 30 min the accumulated amount of lactic acid in the supernatant was measured by analyzing
  • the lactic acid was quantified by the lactic acid specific enzyme assay described above. Known correlation between measured enzyme activity and amount of lactic acid was used to translate measured enzyme activity into the amount of lactic acid present in sample of the supernatant.
  • a compound should lower the lactic acid release in permanent application of at least 50 % in comparison to the untreated biofdm control.
  • Bovine sample disks of about 10 x 10 mm (+/- 2mm) were incubated in a 24 well plate containing 1.8 ml medium in an incubator at 37°C and 60 rpm circular movement.
  • the treatment composition described below were added by pipetting and removed by a suction pump.
  • Fresh medium (MCM-1% sucrose and Treatment Composition (containing typically 0.5 wt.% to 5.0 wt.% of the AACA component)) for another 3-hour incubation.
  • Fresh medium (MCM-1% sucrose and Treatment Composition) for storage for about 14h at 37 °C.
  • Day 2 Fresh medium (MCM-1% sucrose and Treatment Composition) for 2-hour incubation.
  • Fresh medium MCM-1% sucrose and Treatment Composition
  • FAR lactic acid release
  • TCx Treatment Compositions to be used for the Permanent Exposure Procedure were prepared by dissolving the respective ACAA components in a liquid carrier medium (MCM) in the amounts given below in Table 2.
  • MCM liquid carrier medium
  • the Treatment Compositions (TCx) had the following compositions:
  • a negative LAR value indicates a decline and a positive value an increase of lactic acid release from the respective biofdm in comparison to the untreated control biofdm on enamel (lactic acid release of untreated biofdm on enamel is set to 100 %).
  • TCI TCI, TC5, TC7, TC8, TC10, TC11, TC13, TC16, TC17, TC18, TC19, TC20.
  • Certain acetyl amino acid components are effective in lowering the lactic acid release from in vitro human saliva microcosm biofdm whereas others are not effective.

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Abstract

L'invention concerne une composition de soin buccal contenant certains composants d'acide aminé N-acétyle. Les composants d'acide aminé N-acétyle sont utiles dans une méthode de traitement des caries par réduction de la libération d'acide lactique de bactéries libérant de l'acide lactique dans un biofilm buccal dans la bouche d'un homme ou la gueule d'un animal. Le composant acide aminé N-acétyle est choisi parmi les composants acétyle de l'alanine, de la cystéine, de l'acide glutamique, de la glycine, de la leucine, de la proline, de la tyrosine, de l'iso-leucine, du tryptophane, de la phénylalanine et des mélanges de ceux-ci. L'invention concerne également un kit de pièces comprenant une pièce A comprenant l'acide aminé N-acétyle ou le composant, une pièce B comprenant de l'eau et/ou un composant porteur, et éventuellement une pièce C comprenant un dispositif d'application.
PCT/IB2020/061584 2019-12-12 2020-12-07 Composition de soin buccal contenant des composants d'acide aminés n-acétyle pour le traitement des caries WO2021116873A1 (fr)

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WO2024012854A1 (fr) * 2022-07-13 2024-01-18 Unilever Ip Holdings B.V. Composition de soins buccaux

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