EP4065067A1 - Composition de soin buccal contenant des composants d'acide cholique pour le traitement des caries - Google Patents

Composition de soin buccal contenant des composants d'acide cholique pour le traitement des caries

Info

Publication number
EP4065067A1
EP4065067A1 EP20815948.3A EP20815948A EP4065067A1 EP 4065067 A1 EP4065067 A1 EP 4065067A1 EP 20815948 A EP20815948 A EP 20815948A EP 4065067 A1 EP4065067 A1 EP 4065067A1
Authority
EP
European Patent Office
Prior art keywords
cholic acid
acid component
component
amount
oral
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP20815948.3A
Other languages
German (de)
English (en)
Inventor
Ingo Haeberlein
Brenda Schmid
Melanie Hauke
Ajmal SAFI
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
3M Innovative Properties Co
Original Assignee
3M Innovative Properties Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 3M Innovative Properties Co filed Critical 3M Innovative Properties Co
Publication of EP4065067A1 publication Critical patent/EP4065067A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • 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
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/042—Gels
    • 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
    • A61K8/63—Steroids; 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
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • 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
    • 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
    • A61Q11/02—Preparations for deodorising, bleaching or disinfecting dentures
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/48—Thickener, Thickening system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/87—Application Devices; Containers; Packaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/88—Two- or multipart kits
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/92—Oral administration

Definitions

  • the invention relates to an oral care composition containing certain cholic acid components.
  • the oral care compositions and in particular the cholic 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 biofilm 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. l Attempts to influence the formation of biofilm and/or prevent the formation of plaque are described in various documents.
  • WO 03/026601 (LG Household & Health Care) describes an oral care composition for treating sensitive teeth.
  • the oral care composition comprises a potassium phosphate and may further comprise ursodesoxycholic acid in an amount of 0.01 to 1 wt.%.
  • the ursodesoxy cholic acid is added for the purpose of alleviating the inflammation of gums and preventing its recession by weakening the activity of collagenase.
  • fluoride compounds to form fluoride coatings on teeth against e.g. lactic acid produced by bacteria which induce dental caries is proposed.
  • WO 2009/100277 (Colgate-Palmolive) describes a tooth-whitening composition comprising a bleaching agent and a basic amino acid, such as arginine. It is outlined that basic amino acids are metabolized by certain types of bacteria which are not cariogenic and which compete with cariogenic bacteria. The arginolytic bacteria can use arginine to produce ammonia, thereby raising the pH of their environment, while cariogenic bacteria metabolize sugar to produce lactic acid which tends to lower the plaque pH and demineralize teeth.
  • WO 2019/206764 (Unilever) relates to an antiperspirant composition comprising a hydroxy cholic acid, a multivalent metal salt and a topically acceptable carrier.
  • a biofilm 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.
  • the components should not have undesired side effects like bad taste or being astringent.
  • the components of the respective composition should in particular be active if used and/or applied in a permanent treatment.
  • the invention features an oral care composition for treating caries or reducing the risk of getting caries, the oral care composition comprising a cholic acid component contained in a solvent and/or carrier, the cholic acid comprising a cholic acid, chenocholic acid or lithocholic acid moiety, which is optionally elongated at its acid function through an ester or amide function with a spacer moiety comprising a carboxylic, sulfonic, or phosphoric acid function, the respective salts and hydrates thereof.
  • the invention is also related to a kit of parts comprising the oral care composition or the cholic acid component as described in the present text and claims and an application device.
  • Described is also a method of using the cholic 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 cholic acid component in a method for treating caries or reducing the risk of caries, the method comprising the step of bringing the cholic 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).
  • CMC Crohn's disease
  • Cholic acid component is abbreviated as “CHOLA component”.
  • Cholic acid components comprise the following structural element, with R 1 and R 2 being independently selected from H and OH:
  • the “*” indicates the position where the moiety is attached to a further structural element of the cholic acid component.
  • cholic acid components comprise the structural elements of cholic acid (also known as 3a.7a.12a-trihydroxy-5p-cholan-24-oic acid), chenodesoxycholic acid or chenocholic acid (also known as 3a,7a-dihydroxy-5 -cholan-24-oic acid), lithocholic acid (also known as 3a- hydroxy-5 -cholan-24-oic acid), glycocholic acid, (also known as cholylglycine), and taurocholic acid (also as cholaic acid, cholyltaurme, or acidum cholatauricum).
  • the respective salts are called cholates, chenodeoxycholates etc.
  • 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.
  • Consisting essentially of means that specific further components can be present, namely those which do not materially affect the essential characteristic of the article or composition. “Consisting of’ means that no further components should be present.
  • the term “comprise” shall include also the terms “consist essentially of’ and “consists of’.
  • “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.).
  • CHOLA component also includes a composition containing the CHOLA 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 CHOLA component described in the present text using different treating schemes.
  • the CHOLA component functions either as a biofilm metabolism control agent or as an agent for modifying the structure of the biofilm or as a kind of cell membrane modifying agent. Independent of the mechanism, the CHOLA component is effective for treating caries or reducing the risk of getting caries lesions.
  • the cell membrane modifying agent primarily refers to the cell membrane of the cells of the bacteria forming the biofilm and of the extra-cellular membranes constituting the biofilm.
  • the cholic acid components may act as a kind of surfactant.
  • the cholic acid components seem to be able to break down membrane-like structures in oral biofilms and/or may be able to remove enzyme(s) located at these membrane-like structure.
  • the oral care composition described in the present text containing a CHOLA 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 biofilm reducing composition to a composition allowing the control of the metabolic balance on dental plaque.
  • the invention shows that CHOLA components are effective to accomplish caries activity control in a dental biofilm, i.e. being able to influence the metabolic balance of the dental biofilm.
  • the CHOLA component proposed in the present text is easily available at reasonable costs and not harmful to the patient.
  • the CHOLA component is most effective, if it is used in an amount of the critical micelle concentration or above.
  • the CHOLA 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 biofilm of a human or animal being.
  • the CHOLA component comprises a cholic acid moiety as described in the present text.
  • the cholic acid moiety can optionally be elongated at its acid function through an ester or amide function with a spacer moiety comprising a carboxylic, sulfonic, or phosphoric acid function.
  • Orally and/or medically acceptable salts include the Li, Na, K and ammonium salts (such as NHC).
  • the CHOLA component is characterized by the following formula:
  • R 1 and R 2 being independently selected from H, OH,
  • X being selected from O, NH,
  • S being selected from Ci to Cn alkyl or Ci to C7 alkyl, wherein one or more carbon atoms can be replaced by O, S, NH, N + (CH 3 ) 2 ,
  • A being selected from COO, S0 3 , PO4.
  • CHOL being selected from
  • R 1 and R 2 being independently selected from H, OH,
  • X being selected from O, NH,
  • S being selected from Ci to C7 alkyl, wherein one or more carbon atoms can be replaced by O, S, NH, N + (CH 3 ) 2 ,
  • A being selected from COO, SO 3 .
  • CHOLA components were found to be useful: cholate, chenodeoxycholates, lithocholate, glycocholate, taurocholate, taurodeoxycholate, 3-[(3- Cholamidopropyl)dimethylammonio]-l-propanesulfonate, the respective salts and hydrates thereof, in particular the Li, Na, K or ammonium salts and hydrates thereof.
  • Mixtures of the CHOLA components can be used, if desired.
  • the CHOLA component can also be characterized by the following parameters alone or in combination: molecular weight: 380 to 650 g /mol; CMC at 20-25°C: 2 to 350 mM (solvent: water).
  • CHOLA component having a molecular weight in the above range was found to be beneficial because it allows an easier dissolution of the component in a solvent or carrier material. It may also help to facilitate the interaction of the CHOLA component with the cell membranes of the lactic acid reducing bacteria located in a biofilm.
  • CMC critical micelle concentration
  • solubility enhancing moieties such as polar moieties (e.g. ammonium, carboxyl, sulfonium groups) and to use the component in salt form.
  • the CHOLA 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 CHOLA component.
  • Range 0.25 to 10 mmol or 1 to 50 mmol; with respect to 100 g solvent or carrier component.
  • the CHOLA component is used in combination with water.
  • the oral care composition comprises one or more of the CHOLA components and water.
  • Water is used for dissolving or dispersing the CHOLA component, at least partially. Water is typically present in an amount sufficient to fully dissolve the CHOLA component and other optional components being present in the oral care composition.
  • the CHOLA component may be present in the form of micelles.
  • a CHOLA component containing oral care composition may comprise water in the following amounts:
  • the ratio of CHOLA component to water is typically at least 0.001 / 100, or at least 0.01 / 100 with respect to weight.
  • the ratio of CHOLA component to water can be in a range of 0.001 / 100 to 10 / 100, or in a range of 0.01 / 100 to 3 / 100, or in a range of 0.1 / 100 to 2 / 100 with respect to weight.
  • the CHOLA component may also be used in combination with a carrier component.
  • the oral care composition may comprise one or more CHOLA 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 CHOLA 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. If the molecular weight of the film-forming agent is too low, 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 CHOLA 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 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 pyrrolidon, 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 pyrrolidon 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 CHOLA component is used in combination with abrasive particles.
  • the oral care composition may comprise one or more CHOLA components, abrasive particles and optionally carrier component(s) and water.
  • abrasive particles examples include perlite, bentonite, silica, alumina, aluminium hydroxide, ilmenite (FeTiCE), 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 CHOLA component is used in combination with certain amino acids.
  • the oral care composition comprises one or more CHOLA 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) 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, 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 CHOLA 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.
  • the amino acids contained in the CHOLA 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 CHOLA 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.
  • the CHOLA 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 CHOLA component containing 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 CHOLA component containing 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 CHOLA component containing 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 / 1.5 to 100 to 12 / 100, or in a range of 2 to 100 to 10 to 100 with respect to weight.
  • the ratio of CHOLA component to amino acid(s) is typically at least 1 / 500 or at least 1 / 100 or at least 1 / 10.
  • the ratio of CHOLA component to amino acid(s) can be in a range of 1 / 500 to 1 / 1, or in a range 1 / 100 to 1 / 2, or in a range of 1 / 10 to 1 / 5 with respect to weight.
  • the CHOLA 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):
  • 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.
  • a colourant there is no need for a colourant 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 1 wt.% with respect to the whole composition. 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.
  • 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.
  • 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.
  • a CHOLA component containing oral care composition comprises or essentially consists of or consists of: Component A (CHOLA) in an amount of 0.001 to 5 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.
  • a CHOLA containing oral care composition comprises or essentially consists of or consists of:
  • Component A (CHOLA) in an amount of 0.001 to 5 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.
  • a CHOLA containing oral care composition comprises or essentially consists of or consists of:
  • Component A (CHOLA) in an amount of 0.001 to 5 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 CHOLA component described in the present text is particularly useful for producing an oral care composition.
  • the oral care composition containing the CHOLA component described in the present text can typically be produced as follows:
  • the CHOLA 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 CHOLA 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 CHOLA component described in the present text
  • Part B comprising water for dissolving or dispersing the CHOLA 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.
  • CHOLA component containing oral care composition described in the present text in combination with a dental tray, mouth guard or clear tray aligner, providing the CHOLA 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 CHOLA component can be used and applied in different forms or shapes.
  • the CHOLA 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.
  • CHOLA component described in the present text can be used include prophy pastes, prophy powder, varnishes, coatings, etc.
  • the CHOLA 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.
  • 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.
  • CHOLA 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 CHOLA component described in the present text is applied to form a coating or fdm 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 CHOLA component is applied together with film -forming agent(s).
  • Suitable film -forming agents are described above.
  • 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 biofdms 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 to determine the patient-related risk of caries.
  • 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/1 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 risk of caries is.
  • 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 CHOLA 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 CHOLA 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 CHOLA component being applied in combination with water, the CHOLA component being contained in an amount of at least 0.001 wt.% with respect to the weight of the whole composition, the composition having a pH in the range of 6 to 8 and having a viscosity of 1 to 1,000 mPa*s at
  • the CHOLA 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 biofilm in the mouth of a living human or animal, the CHOLA component being applied in combination with water and gel-forming or paste forming component(s), the ratio of the CHOLA component to water being in a range of 0.001: 100 to 5:100 with respect to weight, the 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 CHOLA 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 CHOLA component being applied in combination with water and amino acid(s), the ratio of the CHOLA component to water being in a range of 0.001: 100 to 5:100 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 composition being applied to the oral biofdm for at least 1 min.
  • the CHOLA 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 CHOLA component being applied in combination with water, the ratio of the CHOLA component to water being in a range of 0.001: 100 to 5:100 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 CHOLA 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 CHOLA 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 biofilm in the mouth of a living human or animal, the CHOLA component being applied in combination with water and amino acid(s), the ratio of the CHOLA component to water being in a range of 0.001: 100 to 5: 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 to 10 wt.%; or valine in an amount of
  • the CHOLA 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 biofilm in the mouth of a living human or animal, the CHOLA component being applied in combination with film-forming, gel-forming or paste forming component(s), the CHOLA component being applied to the oral biofilm and/or hard dental tissue for at least 2 days.
  • the CHOLA 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 CHOLA component being selected from cholate , glycocholate taurodeoxycholate , 3 - [(3 -Cholamidopropyl)dimethylammonio] - 1 -propane sulfonate , and mixtures thereof, and being used in combination with water in a ratio of 0.05 to 2% with respect to weight, the method of treating caries or reducing the risk of getting caries comprising the step of bringing the CHOLA 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.
  • compositions can be used in a method or therapy described in the present text.
  • the accumulation of lactic acid in the supernatant (0.75 ml PBS-solution with 5% sucrose per each biofdm sample disc) 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
  • biofdm samples were washed four times with 1.0 ml PBS solution for 30 sec.
  • 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.
  • Negative number indicates that the release of lactic acid was reduced.
  • CMC Critical Micelle Concentration
  • the CMC can be determined by light scattering (increases with concentration of component), surface tension (decreases with concentration of component) and dye solubilization (increases with concentration of component).
  • a simple dye solubilization method for the determination of CMC involves the solubilization of a dye in a detergent solution only in the presence of micelles.
  • the amount of dye is directly proportional to the micelle concentration.
  • the CMC is determined by plotting optical density of the solubilized dye against detergent concentration. The points of inflection on the plot of observed data versus detergent concentration corresponds to the CMC of a typical detergent.
  • 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) for storage for about 14h at 37 °C.
  • the reduction in the lactic acid release should be at least 50 or at least 60%.
  • TCx Treatment Compositions to be used for the Permanent Exposure Procedure and the Periodic Exposure Procedure were prepared by dissolving the respective CHOLA components in a liquid carrier medium (water or MCM) in the amounts given below in Table 2.
  • a liquid carrier medium water or MCM
  • the CHOLA component was dissolved in MCM.
  • the Treatment Compositions (TCx) had the following compositions:
  • Cholic acid components as described in the present text are effective in lowering the lactic acid release from in vitro human saliva microcosm biofilm.
  • the lactic acid release declined to a value close to 100%.

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Abstract

L'invention concerne une composition de soin buccal contenant des composants d'acide cholique. Les composants d'acide cholique 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. Les composants d'acide cholique comprennent un acide cholique, un acide chénocholique ou une fraction d'acide lithocholique, qui est éventuellement allongée au niveau de sa fonction acide par l'intermédiaire d'une fonction ester ou amide avec une fraction d'espaceur comprenant une fonction d'acide carboxylique, sulfonique, ou phosphorique, les sels et hydrates respectifs de ceux-ci; l'invention concerne également un kit de pièces comprenant une partie A comprenant le composant d'acide cholique, une partie B comprenant de l'eau et/ou un composant porteur, et éventuellement une partie C comprenant un dispositif d'application.
EP20815948.3A 2019-11-28 2020-11-24 Composition de soin buccal contenant des composants d'acide cholique pour le traitement des caries Withdrawn EP4065067A1 (fr)

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EP19212149 2019-11-28
PCT/IB2020/061081 WO2021105869A1 (fr) 2019-11-28 2020-11-24 Composition de soin buccal contenant des composants d'acide cholique pour le traitement des caries

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KR100797365B1 (ko) 2001-09-27 2008-01-22 주식회사 엘지생활건강 과민성 치아용 치약 조성물
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