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WO2018058498A1 - Compositions de soins buccaux pour favoriser la santé des gencives - Google Patents

Compositions de soins buccaux pour favoriser la santé des gencives Download PDF

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Publication number
WO2018058498A1
WO2018058498A1 PCT/CN2016/101001 CN2016101001W WO2018058498A1 WO 2018058498 A1 WO2018058498 A1 WO 2018058498A1 CN 2016101001 W CN2016101001 W CN 2016101001W WO 2018058498 A1 WO2018058498 A1 WO 2018058498A1
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WIPO (PCT)
Prior art keywords
oral care
stannous
composition
weight
gum
Prior art date
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Ceased
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PCT/CN2016/101001
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English (en)
Inventor
Ross Strand
Xiujun Xu
Yang Su
Yunming SHI
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Procter and Gamble Co
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Procter and Gamble Co
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Filing date
Publication date
Application filed by Procter and Gamble Co filed Critical Procter and Gamble Co
Priority to PCT/CN2016/101001 priority Critical patent/WO2018058498A1/fr
Priority to EP17854867.3A priority patent/EP3518885A1/fr
Priority to RU2019107279A priority patent/RU2019107279A/ru
Priority to JP2019516677A priority patent/JP6972120B2/ja
Priority to MX2019003040A priority patent/MX383489B/es
Priority to CN201780060532.6A priority patent/CN109789075A/zh
Priority to CA3038231A priority patent/CA3038231A1/fr
Priority to PCT/CN2017/103564 priority patent/WO2018059417A1/fr
Priority to AU2017335795A priority patent/AU2017335795A1/en
Priority to BR112019006331A priority patent/BR112019006331A2/pt
Publication of WO2018058498A1 publication Critical patent/WO2018058498A1/fr
Anticipated expiration legal-status Critical
Priority to AU2020207834A priority patent/AU2020207834B2/en
Ceased legal-status Critical Current

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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
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/20—Halogens; Compounds 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

Definitions

  • tranexamic acid can discolor the oral care compositions, turning them yellow to dark brown, which is undesirable to the consumers.
  • Previous oral care compositions that have described the instability and discoloration issues have formulated with tranexamic acid at higher levels of from 1.5 %to 2 %(see examples in U.S. Patent No. 4,272,513; Gaffar, A., &4,272, 512; Gaffar, A. ) . According to those references, the higher levels are required in order to provide sufficient tranexamic acid efficacy for the wound healing and other benefits.
  • Anti-bacterial agents useful in these other commercially available oral care compositions may include such as, for example: zinc citrate (e.g., Darlie TM Expert toothpaste) , IPMP (e.g., Lion TM Systema toothpaste) , and cetylpyridinium chloride (CPC) .
  • zinc citrate e.g., Darlie TM Expert toothpaste
  • IPMP e.g., Lion TM Systema toothpaste
  • CPC cetylpyridinium chloride
  • these anti-bacterial agents may have poor penetration into the biofilms. As a result, these anti-bacterial agents may simply chemically degrade before being able to interact with bacteria deep in the biofilms. Alternatively, the anti-bacterial agents may exhibit a markedly slow penetration rate into the biofilms. As a result, these anti-bacterial agents may have an inefficient rate of penetration in the biofilms and will take longer to engage and kill the bacteria. It is believed that one or more of these drawbacks render these oral care compositions less efficacious to promote Gum Health, particularly
  • the oral care composition is a dentifrice, and preferably provides pleasant taste and mouth-feel experience. It is yet a further advantage that the oral care compositions have physical and chemical stability across a range of manufacturing, handling and storage conditions. It is yet a further advantage that the oral care compositions have a stable quality of end product (e.g., consistent visual appearance and no discoloration, gingival wound healing performance, etc. ) even after three months storage at 40 °C. It is yet a still further advantage that the oral care compositions of the present invention minimize the use of antibacterial agents. It is yet a still further advantage that the oral compositions of the present invention minimize the amount of the antifibrinolytic agent to reduce and/or eliminate the instability and/or discoloration problems as described above.
  • the above mentioned oral care composition further comprising c) a thickening agent, preferably from 0.01 %to 5 %, preferably from 1 %to 2.5 %, by weight of the composition, of a thickening agent comprising at least one agent, preferably at least two agents, selected from the group consisting of: (i) a linear sulfated polysaccharide; (ii) a natural gum; (iii) a non-ionic cellulose derivative; (iv) a polyvinyl pyrrolidone (PVP) ; (v) polymers comprising at least a a polycarboxylated ethylene backbone; (vi) polyacrylamide; (vii) co-polymers with acrylamide; (viii) pectin; (ix) proteins; (x) polyethylene glycols (PEG) , preferably high molecular weight PEG; and (xi) combinations thereof.
  • a thickening agent preferably from 0.01 %to 5 %, preferably from 1
  • the above mentioned oral care composition further comprising d) from 0 %to less than 0.001 %, by weight of the composition, or preferably is free or substantially free, of folic acid.
  • Figure 1 is a timeline for assessing Mazza indexed bleeding sites for the Assay for Measuring Improve Gingival Wound Healing.
  • Figure 3 is a perspective view of an oral splint with hydroxyapatite ( "HA" ) disks attached thereto.
  • HA hydroxyapatite
  • Figure 4 is a perspective view of the HA disk having grooves therein.
  • Figure 5 is a schematic of a cross sectional view of the groove with biofilm therein.
  • Figure 6 are images of the wound healing of Human Gingival Fibroblasts at 24 hrs post-treatment with Inventive Composition Ex. 2 (containing stannous and TA) or Control Composition Ex. 9 (Sn only) .
  • compositions of the present invention can comprise, consist of, and consist essentially of the essential elements and limitations of the invention described herein, as well as any of the additional or optional ingredients, components, steps, or limitations described herein.
  • Gum Care refers to inherent or promoted benefits of an oral care composition directed, principally, to alleviating one or more symptoms associated with an early stage of gum disease (i.e., gingivitis) .
  • Such symptoms may include, for example bleeding gums; and red, swollen, or tender gums.
  • improve gingival wound healing means reduce gum bleeding in the oral cavity as determined by any generally accepted in vitro or in vivo gum bleeding assay or test or the assay described in Example 11.
  • the term "synergistic Gum Health benefit” as used herein means analytically measurable increases in any two Gum Health benefits that include at least improve gingival wound healing and improve reduction of bacterial activity in the oral cavity, that is more than additive.
  • teeth refers to natural teeth as well as artificial teeth or dental prosthesis.
  • an antifibrinolytic agent preferably tranexamic acid
  • stannous ion i.e., an anti-bacterial agent
  • the surprising discovery was that the penetration of the stannous ion into the biofilms is markedly improved when combined with the tranexamic acid.
  • the tranexamic acid contains both carboxylic and amine groups. It is believed that the stannous ions can bind strongly to these chemical moieties on the tranexamic acid to positively influence the penetration of stannous ions into the biofilms.
  • the penetration depth and/or the penetration rate of stannous ions into the biofilms may be increased, or markedly increased, when formulated with tranexamic acid.
  • the presence of tranexamic acid in combination with stannous ion source in an oral care composition aids the composition's efficacy in mediating the harmful effects of the bacteria in the biofilms on the gums.
  • the present invention is directed to an oral care composition
  • an oral care composition comprising: a) from 0.01 %to 5 %, preferably from 0.05 %to 4 %, by weight of the composition, of a stannous ion source; b) from 0.01 %to 10 %, preferably less than 1 %, by weight of the composition, of an antifibrinolytic agent.
  • the stannous ion source is selected from stannous fluoride, stannous chloride, and combinations thereof. More preferably the stannous ion source comprises stannous chloride.
  • stannous salts are found in U.S. Patent Nos. 5,578,293; Prencipe, M., &5,281,410; Lukacovic, M.F.
  • other ingredients used to stabilize the stannous ions may be included, such as the ingredients described in U.S. Patent Nos. 5,004,597; Majeti, S., &5,578,293; Prencipe, M.
  • the oral care compositions of the present invention may optionally also include other anti-bacterial agents present in an amount of from 0.035 %or more, from 0.05 %to 2 %, from 0.1 %to 1 %, by weight of the composition.
  • these other anti-bacterial agents may include non-cationic anti-bacterial agents such as, for example, halogenated diphenyl ethers, phenolic compounds including phenol and its homologs, mono and poly-alkyl and aromatic halophenols, resorcinol and its derivatives, xylitol, bisphenolic compounds and halogenated salicylanilides, benzoic esters, and halogenated carbanilidies.
  • the present invention further relates to the above mentioned oral care compositions comprising, in a preferred embodiment, an antifibrinolytic agent.
  • an antifibrinolytic agent is a compound of formula (I) :
  • X is a branched or unbranched, saturated or unsaturated, aliphatic group; or an aromatic group.
  • aromatic group refers to an aryl ring and includes, but are not limited to, monocyclic or multi-cyclic hydrocarbon ring system consisting only of hydrogen and carbon and containing from 6 to 18 carbon atoms, where the ring system may be partially saturated. Unless stated otherwise in the specification, the aryl ring is optionally substituted. Aromatic group is intended herein to include, but is not limited to groups such as phenyl, naphthyl, and fluorenyl.
  • cyano refers to the -CN functional group.
  • Alkyl refers to a group containing a straight or branched hydrocarbon chain consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from 1 to 20 carbon atoms, preferably 1 to 12 carbon atoms, preferably 1 to 8, or preferably 1 to 6 carbon atoms, and which is attached to the rest of the molecule by a single bond, e.g., methyl, ethyl, propyl, 1-methylethyl (iso-propyl) , butyl, pentyl, and the like.
  • An alkyl may be optionally substituted.
  • Alkynyl refers to a group containing straight or branched hydrocarbon chain consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, having from 2 to 20 carbon atoms, preferably 2 to 12 carbon atoms, or preferably 1 to 8 carbon atoms, e.g., ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like. An alkynyl may be optionally substituted.
  • Alkylene or “alkylene chain” refers to a group containing straight or branched hydrocarbon chain linking the rest of the molecule to a group, consisting solely of carbon and hydrogen, containing no unsaturation and having from 1 to 12 carbon atoms, e.g., methylene, ethylene, propylene, butylene, and the like. An alkylene may be optionally substituted.
  • alkenylene or alkenylene chain refers to a straight or branched hydrocarbon chain linking the rest of the molecule to a group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon double bond and having from 2 to 20 carbon atoms, preferably 2 to 12 carbon atoms, e.g., ethenylene, propenylene, butenylene, and the like.
  • An alkenylene may be optionally substituted.
  • Cycloalkyl refers to a stable saturated mono-cyclic or polycyclic hydrocarbon group consisting solely of carbon and hydrogen atoms, which may include fused or bridged ring systems, having from 3 to 15 carbon atoms, preferably having from 3 to 10 carbon atoms or preferably from 3 to 7 carbon atoms, e.g., cyclohexane.
  • a cycloalkyl may be optionally substituted.
  • Haloalkyl refers to an alkyl as defined above that is substituted by one or more halogen groups, e.g., trifluoromethyl, difluoromethyl, trichloromethyl, 2, 2, 2-trifluoroethyl, 1, 2-difluoroethyl, 3-bromo-2-fluoropropyl, 1, 2-dibromoethyl, and the like.
  • a haloalkyl may be optionally substituted.
  • Heterocyclyl refers to a stable 3-to 24-membered saturated ring which consists of 2 to 20 carbon atoms and from 1 to 6 heteroatoms selected from atoms consisting of nitrogen, oxygen, or sulfur.
  • the heterocyclyl may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused or bridged ring systems; and the nitrogen, carbon or sulfur atoms in the heterocyclyl may be optionally oxidised; the nitrogen atom may be optionally quaternised.
  • a heterocyclyl may be optionally substituted.
  • Heterocyclylalkyl refers to a functional group of the formula –R a R e where R a is an alkylene as defined above and R e is a heterocyclyl as defined above, and if the heterocyclyl is a nitrogen-containing heterocyclyl, the heterocyclyl may be attached to the alkylene at the nitrogen atom.
  • a heterocyclylalkyl may be optionally substituted.
  • Heteroaryl refers to a 5-to 20-membered aromatic ring which consists of 1 to 17 carbon atoms and from 1 to 3 heteroatoms selected from atoms consisting of nitrogen, oxygen and sulfur.
  • the heteroaryl may be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may include fused or bridged ring systems.
  • a heteroaryl may be optionally substituted.
  • Heteroarylalkyl refers to a functional group of the formula –R a R f where R a is an alkylene as defined above and R f is a heteroaryl as defined above. A heteroarylalkyl may be optionally substituted.
  • the antifibrinolytic agent is selected from tranexamic acid, epsilon aminocaproic acid, p-aminomethylbenzoic acid, or combinations thereof.
  • the antifibrinolytic agent is present in the amount of from 0.1 %to less than 1 %, preferably from 0.2 %to 0.7 %, or more preferably from 0.25 %to 0.55 %, by weight of the composition.
  • the antifibrinolytic agent is tranexamic acid ( "TA" ) , which has the chemical name trans-4-aminomethyl-cyclohexanecarboxylic acid (CAS number 1197-18-8) and the following structural formula (II) :
  • Tranexamic acid is an antifibrinolytic agent used to prevent lysis or dissolution of fibrin clots. It assists in stabilizing fibrin clots, which maintains coagulation and assists in the control of bleeding. Tranexamic acid has been described as non-antibacterial and highly effective for inhibiting gingival inflammation, bleeding, and/or swelling (see U.S. Patent No. 4,272,513; Gaffar, A. ) .
  • the term "tranexamic acid” includes the acid itself or bioprecursors or salts thereof having the desired anti-bleeding activity.
  • tranexamic acid may be employed in free acid form or in the form of an orally acceptable salt thereof, preferably water soluble, such as with an alkali metal (e.g., Na or K) , ammonium, or C 1 -C 8 mono-, di-, or tri-substituted ammonium (e.g., alkanol substituted such as mono-, di-, or tri-ethanolammonium) cation.
  • an alkali metal e.g., Na or K
  • ammonium e.g., ammonium, or C 1 -C 8 mono-, di-, or tri-substituted ammonium (e.g., alkanol substituted such as mono-, di-, or tri-ethanolammonium) cation.
  • Tranexamic acid is commercially available as Alternatively, the tranexamic acid may be synthesized or isolated from cis-trans mixtures thereof (see U.S. Patent No. 3,499,925; Nai
  • tranexamic acid stability and discoloration problems can be resolved by lowering the tranexamic acid concentration in the compositions. It is surprisingly found that only minimal reduction, such as less than 1 %, by weight of the composition, of tranexamic acid can make material differences in its stability and formulation compatibility. The reduced levels of tranexamic acid does not negatively impact its activity and/or efficacy for gingival wound healing due to the effect, potentially synergistic effect, of combining it with stannous ions in preferred oral care compositions of the present invention. Without wishing to be bound by theory, it is believed that stannous ions can bind strongly to these chemical moieties on the tranexamic acid to positively influence the penetration to maintain sufficient efficacy at lower concentrations.
  • the antifibrinolytic agent is epsilon aminocaproic acid ( "EACA" ) .
  • EACA epsilon aminocaproic acid
  • the EACA is present in the amount of from 0.01 %to 5 %, preferably from 0.1 %to 1 %, or more preferably less than 1 %, by weight of the composition.
  • EACA has the chemical name hexanoic acid, 6-amino- (CAS number 60-32-2) and the following structural formula (III) :
  • Epsilon aminocaproic acid and its analogue are commercially available under the tradename
  • the term "epsilon aminocaproic acid” includes the acid itself or bioprecursors or salts thereof having the desired anti-bleeding activity. It is a derivative of the amino acid lysine and is an antiplasmin agent. Similar to tranexamic acid, the use of epsilon aminocaproic acid can also introduce a problem of discoloration into the oral care composition (see U.S. Patent No. 4,649,044; Gomi, T. ) .
  • the liner sulfated polysaccharide is a carrageenan
  • the natural gum is selected from the group consisting of xanthan gum, gum karaya, gum arabic, gum tragacanth, and combinations thereof;
  • non-ionic cellulose or derivative thereof having an average molecular weight range of 50,000 to 1,300,000 Daltons, and preferably an average degree of polymerization from 300 to 4,800;
  • the oral care composition according to the present invention wherein the thickener is selected from the group consisting of: (i) the carrageenan is selected from the group consisting of Kappa-carrageenan, Iota-carrageenan, Lambda-carrageenan, and combinations thereof; (ii) the natural gum is xanthan gum; (iii) the non-ionic cellulose or derivative thereof is hydroxyethyl cellulose ( "HEC” ) ; (iv) the co-polymers of maleic anhydride with methyl vinyl ether are at least one of: Gantrez AN139 (M.W. 500,000 daltons) , Gantrez AN119 (M. W.
  • the homo-polymers of acrylic acid and co-polymers of maleic acid and acrylic acid or methacrylic acid are at least one of: Acusol 445, Acusol 445N, Accusol 531, Acusol 463, Acusol 448, Acusol 460, Acusol 465, Acusol 490, Sokalan CP5, Sokalan CP7, Sokalan CP45, or Sokalan CP12S; and (v) combinations thereof .
  • the GANTREZ TM series of polymers are co-polymers of maleic anhydride with methyl vinyl ether having a molecular weight (M. W. ) of 30,000 daltons to 1,000,000 daltons. These co-polymers are available for example as GANTREZ TM AN139 (M. W. 500,000 daltons) , AN119 (M.W. 250,000 daltons) and S-97 Pharmaceutical Grade (M.W. 70,000 daltons) , from Ashland Chemicals (Kentucky, USA) .
  • the ACUSOL TM and the SOKALAN series of polymers include homopolymers of acrylic acid and copolymers of maleic acid and acrylic acid or methacrylic. Examples are 0: 1000 to 1000: 0 copolymers of maleic acid with acrylic acid having a molecular weight (M.W. ) of about 2,000 to about 1,000,000.
  • M.W. molecular weight
  • copolymers are commercially available as ACUSOL TM 445 and 445N, ACUSOL TM 531, ACUSOL TM 463, ACUSOL TM 448, ACUSOL TM 460, ACUSOL TM 465, ACUSOL TM 497, ACUSOL TM 490 from Dow Chemicals (Michigan, USA) and as CP 5, CP 7, CP 45, and CP 12 S from BASF (New Jersey, USA) .
  • fluoride ions may be selected from a source comprising sodium fluoride, indium fluoride, amine fluoride, sodium monofluorophosphate ("MFP") , potassium fluoride, zinc fluoride, and mixtures thereof.
  • MFP monofluorophosphate
  • the oral care composition may include one or more of an anti-plaque or anti-tartar agent present in the amount of from 0.001 %to 20 %, or from 0.1 %to 5 %, by weight of the composition.
  • an anti-plaque or anti-tartar agent present in the amount of from 0.001 %to 20 %, or from 0.1 %to 5 %, by weight of the composition.
  • Non-limiting examples may include pyrophosphate salt as a source of pyrophosphate ion.
  • Other examples are disclosed in U.S. Patent No. 8,691,190; Haught, J.C., paragraph 55.
  • the pH of the oral care composition may be from 4.5 to 11, or preferably from 5 to 10. Depending upon the actives used in the oral care composition, a different pH may be desired. For formulations containing Stannous Fluoride, it may be desired to have a pH slightly lower than typical dentifrices.
  • the pH is typically measured using a ratio of 1: 3 of paste: water, whereby 1 gram of the oral care composition (e.g., toothpaste) is mixed into 3 grams of deionized water, and then the pH is assessed with a industry accepted pH probe that is calibrated under ambient conditions. The pH is measured by a pH meter with Automatic Temperature Compensating (ATC) probe. The pH meter is capable of reading to 0.001 pH unit.
  • ATC Automatic Temperature Compensating
  • Electrode After each usage the electrode should be washed free from the sample solution with water. Remove any excess water by wiping with a tissue, such as Kimwipes or equivalent. When electrode is not in use, keep electrode tip immersed in pH 7 buffer solution or electrode storage solution. Equipment details are as follows:
  • pH Meter Meter capable of reading to 0.01 or 0.001 pH units.
  • Orion PerpHect combination VWR #34104-843/Orion #8203BN semi-micro, glass body.
  • the oral care compositions herein may include an effective amount of a buffering agent or pH trimming agents, as used herein, refer to agents that can be used to adjust the pH of the oral care compositions to the above-identified pH range.
  • the buffering agents include alkali metal hydroxides, ammonium hydroxide, organic ammonium compounds, carbonates, sesquicarbonates, borates, silicates, phosphates, imidazole, and mixtures thereof.
  • Specific buffering agents include monosodium phosphate (monobasic sodium phosphate) , trisodium phosphate (sodium phosphate tribasic dodecahydrate or TSP) , sodium benzoate, benzoic acid, sodium hydroxide, potassium hydroxide, alkali metal carbonate salts, sodium carbonate, imidazole, pyrophosphate salts, sodium gluconate, lactic acid, sodium lactate, citric acid, sodium citrate, phosphoric acid.
  • monosodium phosphate monobasic sodium phosphate
  • trisodium phosphate sodium phosphate tribasic dodecahydrate or TSP
  • sodium benzoate benzoic acid
  • sodium hydroxide potassium hydroxide
  • alkali metal carbonate salts sodium carbonate
  • imidazole imidazole
  • pyrophosphate salts sodium gluconate
  • lactic acid sodium lactate
  • citric acid sodium citrate
  • phosphoric acid sodium citrate
  • TSP and monosodium phosphate may have calcium ion chelating activity and therefore provide some monofluorophosphate stabilization (in those formulations containing monoflurophospahte) .
  • the oral care composition herein may include from 0.01 %to 5 %, preferably from 0.1 %to 2 %, by weight of the oral care composition, of a flavor composition.
  • suitable flavoring agent that may be used in the flavoring composition include those described in U.S. Patent No. 8,691,190; Haught, J.C., at paragraphs 39 and 40 to 45.
  • the flavor composition comprises:
  • a flavor mixture comprising from greater than 0 %to less than 55 %, or from greater than 65 %to 95 %, by weight of the flavor composition, of methyl salicylcate; from greater than 0 %to less than 30 %, or from greater than 35 %to 65 %, by weight of the flavor composition, of menthol; from greater than 0 %to less than 1 %, or from greater than 5 %to 50 %, by weight of the flavor composition, of eugenol; and from greater than 0 %to less than 3 %, or from greater than 8 %to 30 %, by weight of the flavor composition, of cineol; or
  • the oral care compositions herein may include a sweetening agent.
  • the sweetening agent is generally present in the oral care compositions at levels of from 0.005 %to 5%, by weight of the composition.
  • suitable examples of sweetner include saccharin, dextrose, sucrose, lactose, xylitol, maltose, levulose, aspartame, sodium cyclamate, D-tryptophan, dihydrochalcones, acesulfame, sucralose, neotame, and mixtures thereof.
  • Other suitable examples of sweetener are described in U.S. Patent No. 8,691,190; Haught, J.C.
  • the oral care compositions herein may include a surfactant present in the amount of from 0.1 %to 50 %, from 0.025 %to 9 %, from 0.05 %to 5 %, from 0.1 %to 2.5 %, from 0.5 %to 2 %, or from 0.1 %, to 1 %, by weight of the compositions.
  • the surfactant may be selected from anionic, nonionic, amphoteric, zwitterionic, cationic or mixtures thereof.
  • anionic surfactants may include those described in U.S. Patent No. 8,691,190; Haught, J.C., at paragraphs 32, 33, 34 and 35.
  • Suitable examples of zwitterionic or amphoteric surfactants are described in U.S. Patent No. 8,691,190; Haught, J.C., at paragraph 36, cationic surfactant at paragraph 37, and nonionic surfactants at paragraph 38.
  • the oral care compositions herein may include humectants present in the amount of from 0 %to 70 %, or from 15 %to 55 %, by weight of the compositions. Humectants keep oral care compositions from hardening upon exposure to air and certain humectants may also impart desirable sweetness of flavor to dentifrice compositions. Suitable examples of humectants may include glycerin, sorbitol, polyethylene glycol, propylene glycol, xylitol, trimethyl glycine, and mixtures thereof. Other examples may include other edible polyhydric alcohols.
  • the oral care compositions herein may include an anti-sensitivity agent present in the amount of from 0.001 %to 20 %, or from 0.1 %to 5 %, by weight of the compositions.
  • Suitable examples of anti-sensitivity agent may include those described in U.S. Patent No. 8,926,949; Dayanim, R., at paragraph 41, and U.S. Patent Publication No. 2009/0311200; Lambert, P., at paragraph 59.
  • the oral care compositions herein may include a whitening or oxidizing agent present in the amount of from 0.01 %to 30 %, or from 0.1 %to 10 %, or from 0.5 %to 5 %, by weight of the compositions.
  • Suitable examples may include hydrogen peroxide, urea peroxide, calcium peroxide, sodium peroxide, zinc peroxide, or combinations thereof.
  • Other examples are those described in U.S. Patent No. 8,691,190; Haught, J.C., at paragraph 56.
  • the oral care compositions herein may include an effective amount of an anti-inflammatory agent. Suitable examples may include those described in U.S. Patent Publication No. 2011/0104081, Scott, D.C., at paragraph 55.
  • the oral care compositions herein may include an effective amount of a chelating agent, also referred to as sequestrants, many of which also have anti-calculus activity or tooth substantive activity.
  • a chelating agent also referred to as sequestrants
  • Use of chelating agents in oral care products is advantageous for their ability to complex calcium such as found in the cell walls of bacteria, to disrupt plaque and to complex with metallic ions. Chelation of ions, such as iron or copper, helps retard oxidative deterioration of finished products.
  • Suitable examples of chelating agent may include those described in U.S. Patent Publication No. 2011/0020246; Strand, R., at paragraphs 21 to 28.
  • the oral care compositions herein may include an effective amount of an analgesic or desensitizing agent. Suitable examples may include those described in U.S. Patent No. 9,005,585; Deckner, G. E., at paragraph 117.
  • the present oral care composition can comprise the usual and conventional ancillary components that are known to one skilled in the art. It will be appreciated that selected components for the oral care compositions must be chemically and physically compatible with one another.
  • the present invention relates to a method for cleaning or polishing teeth in a human subject.
  • the method of cleaning or polishing herein comprises contacting a subject's teeth with the oral care compositions according to the present invention.
  • the present invention also relates to a method of promoting Gum Health in a human subject comprising administering to the subject's oral cavity an oral care composition according to the present invention.
  • the method of promoting Gum Health occurs at least within a period selected from the group consisting of:
  • time 0 hours is upon administration of the oral care composition according to the present invention.
  • the present invention also relates to a method of promoting Gum Health, wherein Gum Health is selected from:
  • the methods as described above may be by brushing (e.g., toothbrushing) with an oral care composition (e.g., dentrifice) or rinsing with an oral care composition (e.g., dentifrice slurry or mouthrinse) .
  • the oral care compositions may be applied neat or via a delivery apparatus such as, for example, a toothbrush.
  • Other methods include contacting the topical oral gel, mouthspray, toothpaste, dentifrice, tooth gel, tooth powders, tablets, subgingival gel, foam, mouse, chewing gum, lipstick, sponge, floss, petrolatum gel, or denture product or other form with the subject’s teeth and oral mucosa.
  • the oral care composition may be used as frequently as toothpaste, or may be used less often, for example, weekly, or used by a professional in the form of a prophy paste or other intensive treatment.
  • Examples 1 to 10 are dentifrice compositions shown below with amounts of components in wt%. They may be suitably prepared by conventional methods chosen by the formulator.
  • Examples 1 to 6 are inventive formulations according to the present invention, made with a stannous ion source (e.g., stannous chloride) and a single antifibrinolytic agent (e.g., TA, EACA, or PAMBA) at two concentrations, respectively.
  • Example 7 is an inventive formulation made with stannous chloride and two antifibrinolytic agents (e.g., TA and EACA) .
  • control formulations examples 8-10 are prepared.
  • Example 8 is made without the stannous ion source
  • Example 9 is made without the antifibrinolytic agent
  • Example 10 is made without either components. All of the compositions are prepared by admixture of the components in Tables 1 and 2, in the proportions indicated.
  • subjects who met the study entrance requirement are randomly assigned to treatment or control groups balanced on Baseline Mazza Index scores using a SAS randomization program.
  • Individuals meeting the following criteria are included: be at least 18 years of age; possess a minimum of 12 natural anterior teeth; have at least 5 bleeding sites as measured by Mazza Index at initial visit (i.e., Baseline) ; have gingivitis but not periodontitis; be in good general health as determined by the Investigator/designee based on a review of the medical history/update for participation in the study.
  • Exclusion criteria for individuals includes: severe periodontal disease, as characterized by purulent exudates, generalized mobility, and/or severe recession; any condition which requires antibiotic premedication for the administration of a dental prophylaxis; self-reported pregnancy or intent to become pregnant during the course of the study and nursing females; atypical discoloration or pigmentation in the gingival tissue; fixed facial orthodontic appliances; atypical discoloration or pigmentation in the gingival tissue; use of antibiotics any time during the study; any diseases or conditions that could be expected to interfere with the subject safely completing the study. Clinical parameters for each subject are monitored across the whole study. Individuals that fell into the exclusion criteria are excluded from study participation.
  • Study is 4-week, double-blind and parallel groups. Subjects are treated with products from: the negative control group, the positive control group, and the treatment (i.e., inventive compositions) group.
  • the negative control group receives a regular fluoridated toothpaste product (e.g., 0.321%sodium fluoride- Cavity Protection Product, Lot Number 60771864AA, 2018.03.17) ( "CCP Product” ) .
  • the positive control group receives a marketed traditional Chinese Medicine and TA formulation Yun Nan Bai Yao Liu Lan product, Lot Number 20190408 F05 ( "YNBY Product” ) .
  • the treatment groups received any one of the Inventive Compositions as disclosed in Examples 1-7, which contains a stannous chloride and one or more antifibrinolytic agent (s) .
  • Each of the control or treatment legs are applied topically to the teeth/gingival surface twice daily for period of time of 4 weeks.
  • Mazza Index assessments are performed on the subjects to score for reduction of bleeding sites at Baseline, Day 3 and at 4 weeks (i.e., end of the study) , as shown in Figure 1.
  • the data are analyzed with analysis of covariance ( "ANCOVA” ) , with the respective Baseline as the model covariate using the Statistical Analysis System ( "SAS” ) .
  • the negative control CCP Product which contains no Sn and no TA, shows only modest reduction (i.e., approx. -2 bleeding sites) in the number of bleeding sites over the 4-week study.
  • the results demonstrate that the combination of an antifibrinolytic agent and an anti-bacterial agent (e.g., stannous ion source) provides enhanced gingival anti-bleeding efficacy.
  • the Inventive Composition Ex. 2 demonstrates efficacy at lower levels of antifibrinolytic agents (i.e., 0.50%TA) . This is an advantageous since certain antifibrinolytic agents (e.g., TA, EACA, etc. ) while efficacious are known to cause discoloration and instability issues with the oral care compositions particularly at higher concentrations that have been employed to provide efficacy. Thus, by using lower levels, the discoloration and instability will both be avoided.
  • the following assay is used to assess co-localization percentage of stannous ions with bacteria via in situ plaque biofilms for inventive oral care compositions of the present invention and controls. Details of the assay are described below.
  • HA disks are used for in situ growth of biofilms.
  • the HA disks are designed having three parallel grooves (i.e., 200 ⁇ m wide; 200 ⁇ m deep for two sides'grooves; while 500 ⁇ m wide and 500 ⁇ m deep for the middle groove) in each disk.
  • three parallel grooves i.e., 200 ⁇ m wide; 200 ⁇ m deep for two sides'grooves; while 500 ⁇ m wide and 500 ⁇ m deep for the middle groove.
  • This model allows the collection of undisturbed plaque from the grooves.
  • HA disks are manufactured by Shanghai Bei'erkang biomedicine limited company.

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Abstract

L'invention concerne des compositions de soins buccaux comprenant un agent antifibrinolytique (par exemple, de l'acide tranexamique) et une source d'ions stanneux pour favoriser la santé des gencives d'un consommateur.
PCT/CN2016/101001 2016-09-30 2016-09-30 Compositions de soins buccaux pour favoriser la santé des gencives Ceased WO2018058498A1 (fr)

Priority Applications (11)

Application Number Priority Date Filing Date Title
PCT/CN2016/101001 WO2018058498A1 (fr) 2016-09-30 2016-09-30 Compositions de soins buccaux pour favoriser la santé des gencives
CN201780060532.6A CN109789075A (zh) 2016-09-30 2017-09-27 用于促进牙龈健康的口腔护理组合物
RU2019107279A RU2019107279A (ru) 2016-09-30 2017-09-27 Композиции для ухода за полостью рта для стимулирования здоровья десен
JP2019516677A JP6972120B2 (ja) 2016-09-30 2017-09-27 歯肉健康を促進するための口腔ケア組成物
MX2019003040A MX383489B (es) 2016-09-30 2017-09-27 Composiciones para el cuidado bucal para promover la salud de las encías.
EP17854867.3A EP3518885A1 (fr) 2016-09-30 2017-09-27 Compositions de soins buccaux pour favoriser la santé des gencives
CA3038231A CA3038231A1 (fr) 2016-09-30 2017-09-27 Compositions de soins buccaux pour favoriser la sante des gencives
PCT/CN2017/103564 WO2018059417A1 (fr) 2016-09-30 2017-09-27 Compositions de soins buccaux pour favoriser la santé des gencives
AU2017335795A AU2017335795A1 (en) 2016-09-30 2017-09-27 Oral care compositions for promoting gum health
BR112019006331A BR112019006331A2 (pt) 2016-09-30 2017-09-27 composições para tratamento bucal para promover a saúde das gengivas
AU2020207834A AU2020207834B2 (en) 2016-09-30 2020-07-22 Oral care compositions for promoting gum health

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JP7625843B2 (ja) * 2020-12-14 2025-02-04 ライオン株式会社 口腔用組成物
JP7625844B2 (ja) * 2020-12-14 2025-02-04 ライオン株式会社 口腔用組成物

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JP6972120B2 (ja) 2021-11-24
AU2020207834B2 (en) 2021-10-07
BR112019006331A2 (pt) 2019-07-02
CA3038231A1 (fr) 2018-04-05
RU2019107279A3 (fr) 2020-09-14
MX2019003040A (es) 2019-07-08
WO2018059417A1 (fr) 2018-04-05
AU2020207834A1 (en) 2020-08-13
MX383489B (es) 2025-03-14
CN109789075A (zh) 2019-05-21
AU2017335795A1 (en) 2019-03-14

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