WO2008041055A1 - Compositions d'hygiène buccale stanneuses - Google Patents

Compositions d'hygiène buccale stanneuses Download PDF

Info

Publication number
WO2008041055A1
WO2008041055A1 PCT/IB2006/053598 IB2006053598W WO2008041055A1 WO 2008041055 A1 WO2008041055 A1 WO 2008041055A1 IB 2006053598 W IB2006053598 W IB 2006053598W WO 2008041055 A1 WO2008041055 A1 WO 2008041055A1
Authority
WO
WIPO (PCT)
Prior art keywords
stannous
fluoride
compositions
oral care
poly
Prior art date
Application number
PCT/IB2006/053598
Other languages
English (en)
Inventor
William Michael Glandorf
Donald James White, Jr.
Arif A Baig
Original Assignee
The Procter & Gamble Company
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 The Procter & Gamble Company filed Critical The Procter & Gamble Company
Priority to CNA2006800558505A priority Critical patent/CN101511327A/zh
Priority to JP2009529784A priority patent/JP2010505760A/ja
Priority to EP06809475A priority patent/EP2068814A1/fr
Priority to RU2009111321/15A priority patent/RU2469700C2/ru
Priority to BRPI0622151-3A priority patent/BRPI0622151B1/pt
Priority to PCT/IB2006/053598 priority patent/WO2008041055A1/fr
Priority to CA002663913A priority patent/CA2663913A1/fr
Priority to AU2006349144A priority patent/AU2006349144C1/en
Priority to MX2009003557A priority patent/MX2009003557A/es
Publication of WO2008041055A1 publication Critical patent/WO2008041055A1/fr

Links

Classifications

    • 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
    • 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
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/20—Halogens; Compounds thereof
    • A61K8/21—Fluorides; 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
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/23—Sulfur; Selenium; Tellurium; 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
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/24—Phosphorous; 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
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/26—Aluminium; 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
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/27—Zinc; 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/362—Polycarboxylic acids
    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
    • 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8164—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical, and containing at least one other carboxyl radical in the molecule, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers, e.g. poly (methyl vinyl ether-co-maleic anhydride)
    • 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
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0063—Periodont

Definitions

  • the present invention relates to improved oral compositions containing stannous salts, such as stannous fluoride.
  • stannous salts such as stannous fluoride.
  • These improved compositions provide a spectrum of intraoral benefits derived from stannous fluoride and/or other stannous salt, including antimicrobial effects, control of breath malodor, control of dental plaque growth and metabolism, reduced gingivitis, decreased progression to periodontal disease, reductions in dentinal hypersensitivity, and reduced coronal and root dental caries and erosion.
  • the aforementioned benefits are provided along with significant improvements compared to conventional stannous containing compositions, including: 1) reduced levels of dental staining; T) reduced astringency thereby improving aesthetic characteristics of the compositions; 3) reduction in dental calculus formation, and 4) enhanced stability, bioavailability and thus, efficacy of stannous as antimicrobial, anti-plaque and anti- gingivitis agent.
  • the improved stannous containing compositions provide these benefits through the combined effects of stannous, a second polyvalent cation and mineral surface-active and chelating agents, preferably polymeric and in particular including anionic polymers, such as condensed polyphosphate, polyphosphonate or polycarboxylate.
  • the invention also relates to methods of enhancing therapeutic efficacy while decreasing staining and improving the aesthetic desirability of oral compositions containing stannous salts, such as stannous fluoride.
  • Stannous fluoride is commonly known for its efficacy when formulated into oral products.
  • Stannous fluoride was the first fluoride source incorporated into toothpastes for therapeutic efficacy in the control of dental caries.
  • Stannous fluoride gels, rinses, and dentifrices have since been shown to provide clinical efficacy for the reduction of dental caries, dentinal hypersensitivity, dental plaque and gingivitis.
  • formulations containing stannous fluoride may also help to provide improved breath benefits through chemical and antibacterial actions.
  • Stannous fluoride formulations typically include stabilization systems designed to maintain bioavailable (i.e., soluble and reactive) levels of stannous during shelf storage, accounting for loss of stannous to oxidation or precipitation.
  • stannous fluoride formulations have been formulated with additional stannous containing ingredients, which provide a high concentration of stannous as a reservoir of stannous to maintain clinical efficacy.
  • stannous fluoride compositions are known to be highly effective, successful commercial utilization is complicated by complexity in the development of formulations providing adequate stannous fluoride stability and in the side effects of stannous. Formulations providing increased or improved efficacy typically promote increased side effects. This limits clinical and commercial applications.
  • stannous fluoride is yellow-brown tooth staining. This stain is derived from pellicle, plaque and dietary component reactions with available stannous deposited on tooth surfaces during treatment with effective stannous fluoride formulations.
  • a second side effect routinely encountered during use of effective stannous fluoride formulations is unacceptable formulation astringency.
  • Astringents are locally applied protein precipitants whose low cell permeability restricts actions to cell surfaces and interstitial spaces. Strong astringents can induce contraction and wrinkling of the tissues and mucous secretions can be precipitated or reduced. Within oral products, these chemical actions produce an unpleasant 'drying' sensation in the oral cavity, such as on the tongue, gingival tissues or buccal epithelia.
  • Stannous formulations containing sufficient stannous for bioavailability are routinely described as astringent by patients and consumers and this property is undesirable. The astringency is most noticeable after use of the product.
  • a third side effect of the regular use of stannous fluoride dentifrice compositions is the decreased efficacy in reducing dental calculus with these compositions. It has been established that stannous fluoride dentifrices proven effective for antimicrobial, antigingivitis and other expected benefits do not always show reproducible clinical actions toward the prevention of accumulation of undesirable supragingival dental calculus. The control of supragingival calculus formation along with other clinical benefits is desired by professionals, patients and consumers. The multifunctional activity of oral compositions can simplify hygiene and provide a holistic approach to maintenance therapeutic oral health. Previous attempts to develop effective and consumer acceptable stannous fluoride oral compositions have attempted to solve these cumulative detriments, however none have been fully successful. U.S.
  • patent 5,004,597 issued to Majeti et al., discloses oral compositions containing stannous fluoride and gluconate salts.
  • stannous gluconate results in improved formulation efficacy and stability. While effective, this formulation produces undesirable levels of tooth staining. Moreover, the formulation had unacceptable aesthetics, derived primarily from the astringency of stannous.
  • U.S. patent 5,578,293, issued to Prencipe et al. discloses the use of an organic acid compound to stabilize the stannous ion concentration. Coupled with the stannous fluoride and citrate as the organic acid, the formulations also include soluble pyrophosphate salts.
  • patent 4,323,551 to Parran et al. discloses the use of pyrophosphate salts to provide anticalculus benefits.
  • Clinical research has established the potential of anionic mineral surface-active inhibitors, such as pyrophosphates, in preventing the development of natural and antimicrobial induced tooth staining. (Grossman, Bollmer, Sturzenberger and Vick; Journal of Clinical Dentistry 6(4): 185-187, 1995).
  • all examples include sufficient amount of either citric acid and/or sodium citrate dihydrate to stabilize the stannous ions and to prevent precipitation. These levels also directly inhibit stannous binding to pyrophosphate salts.
  • patent 5,780,015 issued to Fisher et al. discloses the use of dual phase dentifrice containing a potassium salt and a stannous salt wherein hydrogenated castor oil is used to help reduce astringency.
  • the stannous salt is stabilized through the use of an organic acid compound as described in Prencipe et al.
  • Another attempt to produce efficacious stannous composition is described in U.S. patent 5,716,600, issued to Zahradnik et al. This patent discloses low water formulations which help to prevent the stannous fluoride from degradation over time. No attempts are made to reduce the staining of the formulation.
  • U.S. patent 5,017,363, issued to Suhonen discloses a stannous ion chelating copolymer of an alkyl vinyl ether and maleic anhydride or acid in an amount to effectively stabilize stannous ions.
  • Suhonen also discloses that the compositions are substantially free from silica, soluble phosphates such as soluble pyrophosphates (e.g., tetrasodium pyrophosphate and tetrapotassium pyrophosphate), and aldehyde group containing compounds, since the stabilizing function of the stannous ion chelating polymer is not effective in the presence of these ingredients.
  • U.S. patent 5,338,537 discloses the use of a low molecular weight diphosphonic acid, which is used as a binding agent for stannous to help reduce the tendency of staining from the composition. While effective in reducing staining potential, laboratory studies have demonstrated that the antibacterial activity of formulations containing stannous complexed with the low molecular weight diphosphonic acid is very low. Similar results are obtained on formulation with soluble pyrophosphate salts, in the absence of strong citrate chelation, as described above.
  • the present invention relates to oral compositions comprising a stannous ion source, a polyvalent cation source and a mineral surface active agent that binds stannous, said compositions providing enhanced therapeutic efficacy with minimal side effects of tooth staining and astringency.
  • the compositions simultaneously provide reduction and control of supragingival calculus.
  • the mineral surface active agents are agents that are substantive to mineral surfaces such as teeth and additionally have chelating activity for polyvalent cations such as stannous (Sn +2 ), zinc (Zn +2 ), copper (Cu +2 ), aluminum (Al +3 ), iron (Fe +2 , Fe +3 ), strontium (Sr +2 ), calcium (Ca +2 ), barium (Ba +2 ), magnesium (Mg +2 ) and manganese (Mn +2 ).
  • the compositions may also comprise a fluoride ion source.
  • the present oral care compositions may be formulated as single phase or dual phase compositions.
  • the present invention also provides a method for effective delivery of stannous-containing compositions with minimal side effects of tooth staining or astringency and with effective tartar control by administering to a subject a stable dentifrice composition comprising a clinically effective amount of stannous fluoride and/or other stannous salts in combination with a mineral surface active agent, preferably a phosphate- , phosphonate- or carboxy- containing polymer and a polyvalent cation source.
  • a mineral surface active agent preferably a phosphate- , phosphonate- or carboxy- containing polymer and a polyvalent cation source.
  • the word "include,” and its variants, are intended to be non- limiting, such that recitation of items in a list is not to the exclusion of other like items that may also be useful in the materials, compositions, devices, and methods of this invention.
  • the words “preferred”, “preferably” and variants refer to embodiments of the invention that afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances.
  • the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the invention.
  • the oral composition of the present invention may be in the form of a toothpaste, dentifrice, tooth powder, topical oral gel, mouthrinse, denture product, mouthspray, lozenge, oral tablet, or chewing gum.
  • dentifrice means paste, gel, or liquid formulations unless otherwise specified.
  • the dentifrice composition may be in any desired form, such as deep striped, surface striped, multi-layered, having the gel surrounding the paste, or any combination thereof.
  • the oral composition may be a single phase oral composition or may be a combination of the two or more oral compositions, each in a separate phase.
  • single or separate phase herein is meant that all components of each composition are mixed together in one mixture which may contain liquid, solid and gaseous components. Thus each phase may be homogeneous or non-homogeneous.
  • the oral composition is a product, which in the ordinary course of administration, is not intentionally swallowed for purposes of systemic administration of particular therapeutic agents, but is rather retained in the oral cavity for a time sufficient to contact substantially all of the tooth surfaces and/or oral tissues for purposes of oral activity.
  • total composition as used herein means the total composition delivered to the oral cavity, regardless of whether it contains a single phase or multiple phases.
  • each oral composition will be contained in a physically separated compartment of a dispenser and dispensed side-by- side.
  • dispenser means any pump, tube, or container suitable for dispensing toothpaste.
  • orally acceptable carrier includes safe and effective materials for use in the compositions of the present invention.
  • materials are conventional additives in oral care compositions including but not limited to fluoride ion sources, anti-calculus or anti-tartar agents, buffers, abrasives such as silica, bleaching agents such as peroxide sources, alkali metal bicarbonate salts, thickening materials, humectants, water, surfactants, titanium dioxide, flavor system, sweetening agents, xylitol, coloring agents, and mixtures thereof.
  • tartar and “calculus” are used interchangeably and refer to mineralized dental plaque biofilms.
  • stannous as used herein, is defined to mean the stannous that is in a dentifrice or other oral product, and supplied by a source such as stannous salts including stannous fluoride. It may refer to the stannous ions that are provided by a stannous salt other than stannous fluoride, added for stabilization purposes.
  • Active and other ingredients useful herein may be categorized or described herein by their cosmetic and/or therapeutic benefit or their postulated mode of action or function. However, it is to be understood that the active and other ingredients useful herein can, in some instances, provide more than one cosmetic and/or therapeutic benefit or function or operate via more than one mode of action. Therefore, classifications herein are made for the sake of convenience and are not intended to limit an ingredient to the particularly stated application or applications listed.
  • the present invention relates to oral compositions comprising a stannous ion source, a source of polyvalent cations other than stannous and a mineral surface active agent having chelating activity for stannous and polyvalent cations, said compositions providing enhanced therapeutic efficacy from stannous with minimal side effects of tooth staining and astringency.
  • therapeutic efficacy from stannous herein is meant to include antimicrobial effects, control of breath malodor, control of dental plaque growth and metabolism, reduced gingivitis, decreased progression to periodontal disease, and reduction in dentinal hypersensitivity.
  • the compositions preferably comprise a source of fluoride, which may be stannous fluoride, other fluoride salts or combinations thereof.
  • the compositions simultaneously provide reduction and control of supragingival calculus. Reduction of tooth staining and astringency may also enhanced by concurrent appropriate formulation, including utilization of suitable poloxamer ingredients.
  • the mineral surface active agent is preferably polymeric, in particular anionic polymers such as a polyphosphate having an average chain length of about 4 or more, a polyphosphonate, or other phosphate- or phosphonate- or carboxy-containing polymers.
  • anionic polymers such as a polyphosphate having an average chain length of about 4 or more, a polyphosphonate, or other phosphate- or phosphonate- or carboxy-containing polymers.
  • a polymeric binding agent such as a polyphosphate having an average chain length of about 4 or more, would behave similarly to the pyrophosphate or tripolyphosphate in stannous containing dentifrice systems. It has been found that chemical binding or chelation of stannous using pyrophosphate, diphosphonate, or tripolyphosphate to prevent stain formation, also produces unacceptable losses in therapeutic potential.
  • the present oral care compositions may be formulated as single phase or dual phase compositions.
  • One embodiment of the present invention provides a dual phase oral composition comprising a first composition comprising a stannous ion source and a source of polyvalent metal ions other than stannous, preferably zinc, and a second composition comprising a MSA.
  • the MSA in this embodiment may be a linear polyphosphate having an average chain length of about 4 or more ⁇
  • the composition containing the polyphosphate will preferably have a limited water content up to about 20% to minimize hydrolysis of the polyphosphate.
  • a further embodiment of the present invention relates to a single phase oral composition
  • a single phase oral composition comprising a stannous ion source, a source of polyvalent metal ions other than stannous and a MSA such as a linear polyphosphate having an average chain length of about 4 or more.
  • the single -phase composition is formulated such that the linear polyphosphate is stabilized against hydrolytic degradation.
  • the present invention also relates to single phase or dual phase compositions comprising a stannous ion source, a source of polyvalent metal ions other than stannous and an anionic polymer of MW 500 or more containing one or combinations of phosphonate, diphosphonate, and carboxy functionalities.
  • the invention also provides a method for effective delivery of stannous- containing compositions with minimal side effects of tooth staining or astringency and with effective tartar control by administering to a subject a stable dentifrice composition comprising a clinically effective amount of stannous fluoride and/or other stannous salts in combination with a source of polyvalent metal ions other than stannous and a mineral surface-active and chelating agent, such as a phosphate- or phosphonate-containing polymer.
  • a source of polyvalent metal ions other than stannous and a mineral surface-active and chelating agent such as a phosphate- or phosphonate-containing polymer.
  • One method for delivery of this improved stannous oral composition involves application of a dentifrice comprising two dentifrice compositions which are contained in physically separated compartments.
  • Another method involves administering to a subject a stable single-phase dentifrice composition.
  • a stable single phase composition comprises a polyphosphate, or other phosphate- or phosphonate- containing anionic polymer, stannous fluoride as a stannous ion source, a zinc ion source, wherein the composition may have a low total water content, depending upon stability requirements.
  • a preferred method for delivery of the present improved stannous-containing compositions involves application of a dentifrice comprising two dentifrice compositions which are contained in physically separated compartments.
  • the physical separation allows for adequate stabilization of each dentifrice phase and ingredients therein.
  • the chemical interactions of stannous (from stannous fluoride and/or other stannous salt) in one dentifrice phase with the MSA in a separate dentifrice phase allow appropriate delivery of both ingredients, thus, producing full therapeutic activity along with the provision of significant efficacy for the reduction of dental calculus and with marked reductions in undesirable side effects of tooth staining and astringency.
  • the first dentifrice composition will comprise a source of stannous ions while the second dentifrice composition preferably comprises a polyphosphate or other anionic polymer or copolymer containing phosphate, phosphonate, carboxy groups or mixtures thereof.
  • the source of polyvalent cations other than stannous may be incorporated in either or both first and second compositions, depending upon interactions with other components.
  • the present invention includes a stannous ion source as one essential component.
  • the stannous ions are provided from stannous fluoride and/or other stannous salt that are added to the oral composition.
  • Stannous fluoride has been found to help in the reduction of caries, gingivitis, plaque, and sensitivity, and in providing breath benefits.
  • the stannous provided in the oral composition will provide efficacy to a subject using the composition.
  • Other stannous salts include stannous chloride dihydrate, stannous acetate, stannous gluconate, stannous oxalate, stannous sulfate, stannous lactate, and stannous tartrate.
  • the preferred stannous ion sources are stannous fluoride and stannous chloride dihydrate.
  • the combined stannous salts will be present in an amount of from about 0.05% to about 11%, by weight of the total composition.
  • the stannous salts are present in an amount of from about 0.1 to about 7%, more preferably from about 0.4 % to about 3%.
  • Formulations typically include stannous levels, provided by stannous fluoride and other stannous salts, ranging from about 3,000 ppm to about 15,000 ppm stannous ions in the total composition.
  • Dentifrices containing stannous salts are described in U.S. Patent 5,004,597 to Majeti et al. Other descriptions of stannous salts are found in U.S. Patent 5,578,293 issued to Prencipe et al. and in U.S. Patent 5,281,410 issued to Lukacovic et al.
  • stannous salts are found in U.S. Patent 5,578,293 issued to Prencipe et al. and in U.S. Patent 5,281,410 issued to Lukacovic et al.
  • other ingredients needed to stabilize the stannous may be included, such as the ingredients described in Majeti et al. and Prencipe et al.
  • Mineral Surface- Active Agent MSA
  • the present invention includes a mineral surface-active agent (MSA), which has substantivity to teeth and also has chelating or binding activity for stannous and other polyvalent cations.
  • MSA mineral surface-active agent
  • the abbreviation "MSA” herein designates such agents.
  • the "mineral” descriptor is intended to convey that the surface activity or substantivity of the surface-active agent is toward mineral surfaces such as calcium phosphate minerals or teeth.
  • Preferred MSA's are polymeric, in particular polymers containing anionic groups selected from phosphate, phosphonate, carboxy and mixtures thereof. Such anionic functionalities provide these agents with the capability to interact with cationic or positively charged entities.
  • agents show affinity for binding stannous, in particular by stannous ion chelation, as evidenced by ionic fluoride release from stannous fluoride (SnF 2 ) and provision of increased ionic form of fluoride upon binding of the stannous.
  • Effective agents also show surface reactivity toward calcium phosphate minerals, and are thus expected to retard calculus or tartar formation.
  • the agents may also provide stain control, surface conditioning and antierosion benefits. Ideally, these agents will bind the stannous but will still enable the combined mixture to provide the desired tartar control, stain control, and surface conditioning, without having a negative effect on the efficacy of stannous fluoride for the control of dental caries, oral malodor and periodontal diseases including gingivitis.
  • Binding or chelating of stannous by the MSA provides a means of stabilizing stannous particularly in an aqueous environment, wherein stannous can form stannic compounds or can precipitate from solution, thereby reducing the amount of available stannous ions and consequently, the efficacy of the composition.
  • stannous fluoride compositions have been reported to be stabilized by a copolymer of an alkyl vinyl ether and maleic anhydride or acid in U.S. patent 5,017,363, to Suhonen. The copolymers are reported to have the ability to form chelates with the stannous ion which are sufficiently strong to prevent oxidation of stannous or precipitation from solution.
  • the preferred polymeric MSA's will have a strong affinity for enamel surface and will deposit a polymer layer or coating on the enamel surface and produce desired surface protection and conditioning effects.
  • Suitable examples of such polymers are polyelectrolytes such as condensed phosphorylated polymers; polyphosphonates; copolymers of phosphate- or phosphonate-containing monomers or polymers with other monomers such as ethylenically unsaturated monomers and amino acids or with other polymers such as proteins, polypeptides, polysaccharides, poly(acrylate), poly(acrylamide), poly(methacrylate), poly(ethacrylate), poly (hydroxy alky lmethacrylate), poly(vinyl alcohol), poly(maleic anhydride), poly(maleate) poly(amide), poly(ethylene amine), poly(ethylene glycol), poly(propylene glycol), poly(vinyl acetate) and poly(vinyl benzyl chloride); polycarboxylates and carb
  • Suitable polymeric mineral surface active agents include the carboxy-substituted alcohol polymers described in U.S. patents 5,292,501; 5,213,789, 5,093,170; 5,009,882; and 4,939,284; all to Degenhardt et al.; the diphosphonate-derivatized polymers in U.S. patent 5,011,913 to Benedict et al; and the synthetic anionic polymers including polyacrylates and copolymers of maleic anhydride or acid and methyl vinyl ether (e.g., Gantrez), as described, for example, in U.S. Patent 4,627,977, to Gaffar et al.
  • a preferred polymer is diphosphonate modified polyacrylic acid.
  • Polymers with activity have sufficient surface binding propensity to desorb pellicle proteins and remain affixed to enamel surfaces.
  • polymers with end or side chain phosphate or phosphonate functions may both be preferred although other polymers with mineral binding activity may prove effective depending upon adsorption affinity.
  • Suitable phosphonate containing polymeric MSA's include the geminal diphosphonate polymers disclosed as anticalculus agents in US 4,877,603 to Degenhardt et al; phosphonate group containing copolymers disclosed in US 4,749,758 to Dursch et al. and in GB 1,290,724 (both assigned to Hoechst) as suitable for use in detergent and cleaning compositions; and the copolymers and cotelomers disclosed as useful for applications including scale and corrosion inhibition, coatings, cements and ion-exchange resins in US 5,980,776 to Zakikhani et al. and in US 6,071,434 to Davis et al.
  • Preferred polymers include the water-soluble copolymers of vinylphosphonic acid and acrylic acid and salts thereof disclosed in GB 1,290,724 wherein the copolymers contain from about 10% to about 90% by weight vinylphosphonic acid and from about 90% to about 10% by weight acrylic acid, more particularly wherein the copolymers have a weight ratio of vinylphosphonic acid to acrylic acid of 70% vinylphosphonic acid to 30% acrylic acid; 50% vinylphosphonic acid to 50% acrylic acid; or 30% vinylphosphonic acid to 70% acrylic acid.
  • Suitable polymers include the diphosphonate/acrylate polymers supplied by Rhodia under the designation ITC 1087 (Average MW 3000-60,000) and Polymer 1154 (Average MW 6000-55,000).
  • a preferred MSA will be stable with other components of the formulation such as ionic fluoride and will not hydrolyze in high water content formulations, thus permitting a simple single phase dentifrice or mouthrinse formulation. If the MSA's does not have these stability properties, one option is to formulate a dual phase formulation with the MSA's physically separated from the incompatible component(s).
  • a preferred polymeric MSA is a polyphosphate.
  • a polyphosphate is generally understood to consist of two or more phosphate molecules arranged primarily in a linear configuration, although some cyclic derivatives may be present. Particularly effective are polyphosphates having an average chain length of about four or more phosphate groups so that surface adsorption at effective concentrations produces sufficient non- bound phosphate functions which enhance the anionic surface charge as well as hydrophilic character of the surfaces.
  • the pyrophosphates and tripolyphosphates are discussed separately under additional anticalculus agents.
  • the longer-chain polyphosphate salts include tetrapolyphosphate and hexametaphosphate, among others. Polyphosphates larger than tetrapolyphosphate usually occur as amorphous glassy materials. Examples of suitable polyphosphates are the linear "glassy" polyphosphates having the formula:
  • X0(XP0 3 ) n X wherein X is sodium, potassium or ammonium and n averages from about 6 to about 125.
  • polyphosphates with an average chain length greater than about 4 will react with ionic fluoride in oral compositions at ambient temperature and produce monofluorophosphate ions, in addition to altering the pH of the composition. This reaction compromises the efficacy of the oral composition and its ability to provide stable ionic fluoride and polyphosphate to the oral surfaces. It is also known that polyphosphates undergo hydrolysis. Therefore, formulating with such polyphosphates presents some difficulties. One way to stabilize the polyphosphate from hydrolysis and/or interaction with incompatible ingredients is to reduce the total water content of the dentifrice composition. U.S. patent 5,939,052 issued to White, Jr. et al. further describes the polyphosphates. The phosphate sources are also described in more detail in Kirk-Othmer Encyclopedia of Chemical Technology, Fourth Edition, Volume 18, Wiley-Interscience Publishers (1996).
  • an ideal the ratio of total moles of phosphate anion to total moles of stannous ion has been found to be a molar ratio of phosphate anion to stannous ion of from about 0.2:1 to about 5:1, preferably from about 0.5:1 to about 3:1, more preferably from about 0.6:1 to about 2:1, and most preferably from about 0.7:1 to about 1:1.
  • polyphosphorylated compounds may be used as the MSA/chelant in addition to or instead of the polyphosphate, in particular polyphosphorylated inositol compounds such as phytic acid, myo-inositol pentakis(dihydrogen phosphate); myoinositol tetrakis(dihydrogen phosphate), myo-inositol trikis(dihydrogen phosphate), and an alkali metal, alkaline earth metal or ammonium salt thereof.
  • polyphosphorylated inositol compounds such as phytic acid, myo-inositol pentakis(dihydrogen phosphate); myoinositol tetrakis(dihydrogen phosphate), myo-inositol trikis(dihydrogen phosphate), and an alkali metal, alkaline earth metal or ammonium salt thereof.
  • phytic acid also known as myo-inositol 1,2,3,4,5, 6-hexakis (dihydrogen phosphate) or inositol hexaphosphoric acid, and its alkali metal, alkaline earth metal or ammonium salts.
  • phytate includes phytic acid and its salts as well as the other polyphosphorylated inositol compounds.
  • MSA's that may be used are chelating materials that have been suggested in the art for the purpose of retarding calculus formation and removing calculus after it is formed.
  • the chemical approach to calculus inhibition generally involves chelation of calcium ion and/or crystal growth inhibition which prevents the calculus from forming and/or breaks down mature calculus by removing calcium.
  • These chemical chelants are discussed in more detail below under the section on Anticalculus Agents.
  • the amount of MSA required is an effective amount which will bind the stannous, permit adequate antimicrobial activity, reduce dental stain and formulation astringency, and be capable of reducing dental calculus.
  • An effective amount of MSA will typically be from about 0.05% to about 35%, preferably from about 1% to about 30%, more preferably from about 5% to about 25%, and most preferably from about 6% to about 20%, by weight of the total oral composition.
  • MSA/chelating agents In addition to binding stannous ions effectively, some of the MSA/chelating agents have been found useful as solubilizing agents for insoluble components of the composition.
  • Glass H polyphosphate has been found to solubilize insoluble stannous salts as well as stannous oxides and hydroxides.
  • compositions preferably comprise a source of polyvalent cations other than stannous, including inorganic ions such as zinc (Zn +2 ), copper (Cu +2 ), aluminum (Al +3 ), iron (Fe +2 , Fe +3 ), strontium (Sr +2 ), calcium (Ca +2 ), barium (Ba +2 ), magnesium (Mg +2 ) and manganese (Mn +2 ).
  • inorganic ions such as zinc (Zn +2 ), copper (Cu +2 ), aluminum (Al +3 ), iron (Fe +2 , Fe +3 ), strontium (Sr +2 ), calcium (Ca +2 ), barium (Ba +2 ), magnesium (Mg +2 ) and manganese (Mn +2 ).
  • inorganic ions such as zinc (Zn +2 ), copper (Cu +2 ), aluminum (Al +3 ), iron (Fe +2 , Fe +3 ), strontium (Sr +2
  • the polyvalent cation source is typically present at a level sufficient to supply a molar ratio of polyvalent cation to stannous preferably 1:1 or greater. This ensures a sufficient concentration of other polyvalent cation to compete with stannous for the MSA.
  • the level of other polyvalent cations is of course also dependent on secondary considerations such as aesthetics and stability of the compositions and may be lower than the preferred 1:1 ratio.
  • Preferred polyvalent cations are inorganic cations supplied from salts such as nitrate, chloride, fluoride, phosphate, pyrophosphate, polyphosphate, sulfate, carbonate, citrate, lactate, and oxalate or from oxides or hydroxides.
  • the polyvalent cation source may be water soluble, sparingly-soluble or insoluble.
  • the composition comprises stannous fluoride as a source of stannous, a zinc salt as a source of zinc ions and a polyphosphate as MSA/chelant.
  • the composition may be formulated as a single phase product or a two- phase product with stannous fluoride and the zinc salt in a first composition and the polyphosphate MSA in a second composition.
  • the second composition comprises a copolymer of maleic anhydride or acid and methyl vinyl ether (Gantrez) as MSA.
  • the preferred molar ratio of zinc ions to stannous ions ranges from about 0.5:1 to about 5:1.
  • the composition which may be single-phase or dual- phase, comprises a calcium salt as a source of calcium ions, stannous fluoride as the source of stannous and fluoride and as MSA, a polyphosphate, a copolymer of maleic anhydride or acid and methyl vinyl ether or mixtures thereof .
  • a dual-phase composition comprises stannous fluoride in a first composition and calcium chloride and MSA in a second composition.
  • compositions In preparing the present compositions, it is desirable to add one or more carrier materials or excipients to the compositions. Such materials are well known in the art and are readily chosen by one skilled in the art based on the physical, aesthetic and performance properties desired for the compositions being prepared. These carriers may be included at levels typically from about 50% to about 99%, preferably from about 70% to about 98%, and more preferably from about 90% to about 95%, by weight of the oral composition. Examples of such optional carriers are described in the following paragraphs.
  • Water employed in the preparation of commercially suitable oral compositions should preferably be of low ion content and free of organic impurities.
  • water may comprise from 0% up to about 95%, and preferably from about 5% to about 50%, by weight of the composition herein. This water content may be in a single phase oral composition or may be the resulting total water content of a dual phase oral composition.
  • the oral composition comprises a polyphosphate having an average chain length of about 4 or more
  • the composition or phase containing the polyphosphate will comprise a lower level of water, generally up to about 20% total water.
  • the total water content is from about 2% to about 20%, more preferably from about 4% to about 15%, and most preferably from about 5% to about 12%, by weight of the oral composition.
  • the amounts of water include the free water which is added plus that which is introduced with other materials, such as with sorbitol, silica, surfactant solutions, and/or color solutions.
  • Buffering Agent include the free water which is added plus that which is introduced with other
  • the present compositions may contain a buffering agent.
  • Buffering agents refer to agents that can be used to adjust the pH of the compositions to a range of about pH 3.0 to about pH 10.
  • the phase of the oral composition containing stannous will typically have a slurry pH of from about 3.0 to about 7.0, preferably from about 3.25 to about 6.0, and more preferably from about 3.5 to about 5.5.
  • the phase containing the MSA/chelating agent will typically have a slurry pH of from about 4.0 to about 10, preferably from about 4.5 to about 8, and more preferably from about 5.0 to about 7.0.
  • An oral composition containing both stannous and a MSA/chelating agent in a single phase will typically have a pH of from about 4 to about 7, preferably from about 4.5 to about 6.5, and more preferably from about 5 to about 6.
  • Suitable buffering agents include alkali metal hydroxides, carbonates, sesquicarbonates, borates, silicates, phosphates, imidazole, and mixtures thereof.
  • Specific buffering agents include monosodium phosphate, trisodium phosphate, sodium benzoate, benzoic acid, sodium hydroxide, potassium hydroxide, alkali metal carbonate salts, sodium carbonate, imidazole, pyrophosphate salts, citric acid, and sodium citrate.
  • Preferred buffers would be those that control the pH in the target range without complexing stannous ions.
  • Preferred buffering agents include acetic acid, sodium acetate, citric acid, sodium citrate, benzoic acid and sodium benzoate. Buffering agents are used at a level of from about 0.1% to about 30%, preferably from about 1% to about 10%, and more preferably from about 1.5% to about 3%, by weight of the present composition.
  • the oral compositions of the present invention will optionally include a soluble fluoride source capable of providing bioavailable and efficacious fluoride ions.
  • Soluble fluoride ion sources include sodium fluoride, stannous fluoride, indium fluoride, amine fluoride and sodium monofluorophosphate.
  • Stannous fluoride is a preferred soluble fluoride source. This ingredient may serve as both a/the stannous source and fluoride source.
  • the present compositions may contain a soluble fluoride ion source capable of providing from about 50 ppm to about 3500 ppm, and preferably from about 500 ppm to about 3000 ppm of free fluoride ions.
  • fluoride ion sources may be present in the total oral composition at an amount of from about 0.1% to about 5%, preferably from about 0.2% to about 1%, and more preferably from about 0.3% to about 0.6%, by weight of the total composition delivered to the oral cavity.
  • Chelating agents are able to complex calcium found in the cell walls of the bacteria and can also disrupt plaque by removing calcium from the calcium bridges which help hold this biomass intact. However, it is not desired to use a chelating agent which has an affinity for calcium that is too high, as this may result in tooth demineralization, which is contrary to the objects and intentions of the present invention. Suitable chelating agents will generally have a calcium binding constant of about 10 1 to 10 5 to provide improved cleaning with reduced plaque and calculus formation. Chelating agents also have the ability to complex with metallic ions and thus can be used for stannous stabilization.
  • Such chelating agents useful for their anticalculus activity include pyrophosphates, tripolyphosphates, and diphosphonates such as EHDP and AHP.
  • the pyrophosphate salts useful as a source of pyrophosphate ion in the present compositions include the dialkali metal pyrophosphate salts, tetraalkali metal pyrophosphate salts, and mixtures thereof. Disodium dihydrogen pyrophosphate (Na2H2P2 ⁇ 7), tetrasodium pyrophosphate (Na4P2U7), and tetrapotassium pyrophosphate (K4P2O7) in their unhydrated as well as hydrated forms are the preferred species.
  • the pyrophosphate salt may be present in one of three ways: predominately dissolved, predominately undissolved, or a mixture of dissolved and undissolved pyrophosphate.
  • compositions comprising predominately dissolved pyrophosphate refer to compositions where at least one pyrophosphate ion source is in an amount sufficient to provide at least about 1.0% free pyrophosphate ions.
  • the amount of free pyrophosphate ions may be from about 1% to about 15%, from about 1.5% to about 10% in one embodiment, and from about 2% to about 6% in another embodiment.
  • Free pyrophosphate ions may be present in a variety of protonated states depending on the pH of the composition.
  • compositions comprising predominately undissolved pyrophosphate refer to compositions containing no more than about 20% of the total pyrophosphate salt dissolved in the composition, preferably less than about 10% of the total pyrophosphate dissolved in the composition.
  • Tetrasodium pyrophosphate salt is the preferred pyrophosphate salt in these compositions.
  • Tetrasodium pyrophosphate may be the anhydrous salt form or the decahydrate form, or any other species stable in solid form in the dentifrice compositions.
  • the salt is in its solid particle form, which may be its crystalline and/or amorphous state, with the particle size of the salt preferably being small enough to be aesthetically acceptable and readily soluble during use.
  • compositions may also comprise a mixture of dissolved and undissolved pyrophosphate salts. Any of the above mentioned pyrophosphate salts may be used.
  • chelating agents used as anticalculus agent include ethylenediaminetetraacetic acid, nitrilotriacetic acid and related compounds disclosed in British Patent 490,384, Feb. 15, 1937; polyphosphonates in U.S. Pat. No. 3,678,154, JuI. 18, 1972 to Widder et al., U.S. Pat. No. 5,338,537 issued to August 16, 1994 to White, Jr., and US Pat. No. 5,451,401 issued Sep. 19, 1995 to Zerby et al.; carbonyl diphosphonates in U.S. Pat. No. 3,737,533, Jun.
  • chelating agents that may be used as anticalculus agents include gluconic acid, tartaric acid, citric acid and pharmaceutically-acceptable salts thereof. Examples include sodium or potassium gluconate and citrate; citric acid/alkali metal citrate combination; zinc citrate trihydrate; disodium tartrate; dipotassium tartrate; sodium potassium tartrate; sodium hydrogen tartrate; potassium hydrogen tartrate.
  • the amounts of such chelating agents suitable for use in the present invention are about 0.1% to about 2.5%, preferably from about 0.5% to about 2.5% and more preferably from about 1.0% to about 2.5%.
  • Still other anticalculus agents suitable for use in the present invention are the polymeric polycarboxylates disclosed in U.S.
  • Patent 4,138,477, February 6, 1979 and U.S. Patent 4,183,914, January 15, 1980 to Gaffar et al. include copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer, such as methyl vinyl ether (methoxy ethylene), styrene, isobutylene or ethyl vinyl ether.
  • methyl vinyl ether methoxy ethylene
  • styrene isobutylene or ethyl vinyl ether.
  • Such materials are well known in the art, being employed in the form of their free acids or partially or preferably fully neutralized water soluble alkali metal (e.g. potassium and preferably sodium) or ammonium salts.
  • Examples are 1:4 to 4:1 copolymers of maleic anhydride with methyl vinyl ether having a molecular weight (M.W.) of about 30,000 to about 1,000,000. These copolymers are available for example as Gantrez AN 139 (M.W. 500,000), AN 119 (M.W. 250,000) and S-97 Pharmaceutical Grade (M.W. 70,000), of GAF Chemicals Corporation.
  • operative polymeric polycarboxylates include the 1:1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone, or ethylene, the latter being available for example as Monsanto EMA No. 1103, M.W. 10,000 and EMA Grade 61, and 1: 1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2- pyrrolidone.
  • Abrasive Polishing Materials include the 1:1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone, or ethylene, the latter being available for example as Monsanto EMA No. 1103, M.W. 10,000 and EMA Grade 61, and 1: 1 copolymers of acrylic acid with methyl or
  • an abrasive polishing material may also be included in the oral compositions.
  • the abrasive polishing material contemplated for use in the compositions of the present invention can be any material which does not excessively abrade dentin.
  • the abrasive polishing material should be formulated in the oral composition so that it does not compromise the stability of the stannous or fluoride.
  • the abrasive polishing material is preferably in a separate phase from the fluoride ion source and stannous ion source.
  • Typical abrasive polishing materials include silicas including gels and precipitates; aluminas; phosphates including orthophosphates, polymetaphosphates, and pyrophosphates; and mixtures thereof. Specific examples include dicalcium orthophosphate dihydrate, calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphate, insoluble sodium polymetaphosphate, hydrated alumina, beta calcium pyrophosphate, calcium carbonate, and resinous abrasive materials such as particulate condensation products of urea and formaldehyde, and others such as disclosed by Cooley et al in U.S. Patent 3,070,510, issued Dec. 25, 1962. Mixtures of abrasives may also be used. If the oral composition or particular phase comprises a polyphosphate having an average chain length of about 4 or more, calcium containing abrasives and alumina are not preferred abrasives. The most preferred abrasive is silica.
  • Silica dental abrasives of various types are preferred because of their unique benefits of exceptional dental cleaning and polishing performance without unduly abrading tooth enamel or dentine.
  • the silica abrasive polishing materials herein, as well as other abrasives generally have an average particle size ranging between about 0.1 to about 30 microns, and preferably from about 5 to about 15 microns.
  • the abrasive can be precipitated silica or silica gels such as the silica xerogels described in Pader et al., U.S. Patent 3,538,230, issued Mar. 2, 1970, and DiGiulio, U.S. Patent 3,862,307, issued Jan. 21, 1975.
  • silica xerogels marketed under the trade name "Syloid" by the W.R. Grace & Company, Davison Chemical Division.
  • precipitated silica materials such as those marketed by the J. M. Huber Corporation under the trade name, "Zeodent", particularly the silica carrying the designation "Zeodent 119".
  • the types of silica dental abrasives useful in the toothpastes of the present invention are described in more detail in Wason, U.S. Patent 4,340,583, issued July 29, 1982. Other suitable silica abrasives are described in Rice, U.S.
  • the abrasive in the oral composition compositions described herein is generally present at a level of from about 6% to about 70% by weight of the composition.
  • oral compositions contain from about 10% to about 50% of abrasive, by weight of the oral composition.
  • the present invention may include a peroxide source in the composition.
  • the peroxide source is selected from the group consisting of hydrogen peroxide, calcium peroxide, urea peroxide, and mixtures thereof.
  • the preferred peroxide source is calcium peroxide.
  • the peroxide source is not in the same phase as the stannous ion source.
  • the following amounts represent the amount of peroxide raw material, although the peroxide source may contain ingredients other than the peroxide raw material.
  • the present composition may contain from about 0.01% to about 10%, preferably from about 0.1% to about 5%, more preferably from about 0.2% to about 3%, and most preferably from about 0.3% to about 0.8% of a peroxide source, by weight of the oral composition.
  • the present invention may also include an alkali metal bicarbonate salt.
  • Alkali metal bicarbonate salts are soluble in water and unless stabilized, tend to release carbon dioxide in an aqueous system.
  • the alkali metal bicarbonate salt also functions as a buffering agent. Because of the pH at which alkali metal bicarbonate salts buffer, the bicarbonate salt is preferably in a phase separate from the stannous ion source.
  • the present composition may contain from about 0.5% to about 50%, preferably from about 0.5% to about 30%, more preferably from about 2% to about 20%, and most preferably from about 5% to about 18% of an alkali metal bicarbonate salt, by weight of the oral composition. Additional Carriers
  • compositions are in the form of toothpastes, dentifrices, topical oral gels, mouthrinse, denture product, mouthsprays, lozenges, oral tablets or chewing gums and typically contain some thickening material or binders to provide a desirable consistency.
  • the amount and type of the thickening material will depend upon the form of the product.
  • Preferred thickening agents are carboxy vinyl polymers, carrageenan, hydroxyethyl cellulose, and water soluble salts of cellulose ethers such as sodium carboxymethylcellulose and sodium hydroxyethyl cellulose.
  • Natural gums such as gum karaya, xanthan gum, gum arabic, and gum tragacanth can also be used.
  • Colloidal magnesium aluminum silicate or finely divided silica can be used as part of the thickening agent to further improve texture.
  • Thickening agents can be used in an amount from about 0.1% to about 15%, by weight of the oral composition.
  • humectant Another optional component of the compositions desired herein is a humectant.
  • the humectant serves to keep oral compositions from hardening upon exposure to air and certain humectants can also impart desirable sweetness of flavor to toothpaste compositions.
  • Suitable humectants for use in the invention include glycerin, sorbitol, polyethylene glycol, propylene glycol, xylitol, and other edible polyhydric alcohols.
  • the humectant generally comprises from about 0% to 70%, and preferably from about 15% to 55%, by weight of the oral composition.
  • compositions may also comprise surfactants, also commonly referred to as sudsing agents.
  • Suitable surfactants are those which are reasonably stable and foam throughout a wide pH range.
  • the surfactant may be anionic, nonionic, amphoteric, zwitterionic, cationic, or mixtures thereof.
  • Anionic surfactants useful herein include the water-soluble salts of alkyl sulfates having from 8 to 20 carbon atoms in the alkyl radical (e.g., sodium alkyl sulfate) and the water-soluble salts of sulfonated monoglycerides of fatty acids having from 8 to 20 carbon atoms.
  • anionic surfactants of this type.
  • Other suitable anionic surfactants are sarcosinates, such as sodium lauroyl sarcosinate, taurates, sodium lauryl sulfoacetate, sodium lauroyl isethionate, sodium laureth carboxylate, and sodium dodecyl benzenesulfonate. Mixtures of anionic surfactants can also be employed.
  • Many suitable anionic surfactants are disclosed by Agricola et al., U.S. Patent 3,959,458, issued May 25, 1976.
  • Nonionic surfactants which can be used in the compositions of the present invention can be broadly defined as compounds produced by the condensation of alkylene oxide groups (hydrophilic in nature) with an organic hydrophobic compound which may be aliphatic or alkyl- aromatic in nature.
  • nonionic surfactants include poloxamers (sold under trade name Pluronic), polyoxyethylene, polyoxyethylene sorbitan esters (sold under trade name Tweens), Polyoxyl 40 hydrogenated castor oil, fatty alcohol ethoxylates, polyethylene oxide condensates of alkyl phenols, products derived from the condensation of ethylene oxide with the reaction product of propylene oxide and ethylene diamine, ethylene oxide condensates of aliphatic alcohols, long chain tertiary amine oxides, long chain tertiary phosphine oxides, long chain dialkyl sulfoxides, and mixtures of such materials.
  • Pluronic poloxamers
  • polyoxyethylene polyoxyethylene
  • polyoxyethylene sorbitan esters sold under trade name Tweens
  • Polyoxyl 40 hydrogenated castor oil Polyoxyl 40 hydrogenated castor oil
  • fatty alcohol ethoxylates polyethylene oxide condensates of alkyl phenols, products derived from the condensation of
  • the nonionic surfactant poloxamer 407 is one of the most preferred surfactant because the poloxamer has been discovered to help reduce the astringency of the stannous.
  • the amphoteric surfactants useful in the present invention can be broadly described as derivatives of aliphatic secondary and tertiary amines in which the aliphatic radical can be a straight chain or branched and wherein one of the aliphatic substituents contains from about 8 to about 18 carbon atoms and one contains an anionic water-solubilizing group, e.g., carboxylate, sulfonate, sulfate, phosphate, or phosphonate.
  • amphoteric surfactants are betaines, specifically cocamidopropyl betaine. Mixtures of amphoteric surfactants can also be employed. Many of the suitable nonionic and amphoteric surfactants are disclosed by Gieske et al., U.S. Patent 4,051,234, issued September 27, 1977.
  • the present composition typically comprises one or more surfactants each at a level of from about 0.25% to about 12%, preferably from about 0.5% to about 8%, and most preferably from about 1% to about 6%, by weight of the composition.
  • Titanium dioxide may also be added to the present composition. Titanium dioxide is a white powder which adds opacity to the compositions. Titanium dioxide generally comprises from about 0.25% to about 5%, by weight of the composition.
  • Coloring agents may also be added to the present composition.
  • the coloring agent may be in the form of an aqueous solution, preferably 1% coloring agent in a solution of water.
  • Color solutions generally comprise from about 0.01% to about 5%, by weight of the composition.
  • a flavor system can also be added to the compositions.
  • suitable flavoring components include oil of wintergreen, oil of peppermint, oil of spearmint, clove bud oil, menthol, anethole, methyl salicylate, eucalyptol, cassia, 1-menthyl acetate, sage, eugenol, parsley oil, oxanone, alpha-irisone, marjoram, lemon, orange, propenyl guaethol, cinnamon, vanillin, ethyl vanillin, heliotropine, 4-cis-heptenal, diacetyl, methyl-para-tert-butyl phenyl acetate, and mixtures thereof.
  • Coolants may also be part of the flavor system.
  • Preferred coolants in the present compositions are the paramenthan carboxyamide agents such as N-ethyl-p-menthan-3-carboxamide (known commercially as "WS-3") and mixtures thereof.
  • a flavor system is generally used in the compositions at levels of from about 0.001% to about 5%, by weight of the composition.
  • Sweetening agents can be added to the compositions. These include saccharin, dextrose, sucrose, lactose, xylitol, maltose, levulose, aspartame, sodium cyclamate, D- tryptophan, dihydrochalcones, acesulfame, and mixtures thereof.
  • Various coloring agents may also be incorporated in the present invention. Sweetening agents and coloring agents are generally used in toothpastes at levels of from about 0.005% to about 5%, by weight of the composition.
  • the present invention may also include other agents in addition to the stannous to provide antimicrobial benefits. These agents may be included at levels which do not prevent the interaction between stannous and the MSA.
  • water insoluble non-cationic antimicrobial agents such as halogenated diphenyl ethers, phenolic compounds including phenol and its homologs, mono and poly-alkyl and aromatic halophenols, resorcinol and its derivatives, bisphenolic compounds and halogenated salicylanilides, benzoic esters, and halogenated carbanilides.
  • the water soluble antimicrobials include quaternary ammonium salts and bis-biquanide salts, among others. Triclosan monophosphate is an additional water soluble antimicrobial agent.
  • the quaternary ammonium agents include those in which one or two of the substitutes on the quaternary nitrogen has a carbon chain length (typically alkyl group) from about 8 to about 20, typically from about 10 to about 18 carbon atoms while the remaining substitutes (typically alkyl or benzyl group) have a lower number of carbon atoms, such as from about 1 to about 7 carbon atoms, typically methyl or ethyl groups.
  • Specific antimicrobial agents include chlorhexidine, triclosan, triclosan monophosphate, and flavor oils such as thymol.
  • Triclosan and other agents of this type are disclosed in U.S. Patent 5,015,466, issued to Parran, Jr. et al. and U.S. Patent 4,894,220, to Nabi et al.
  • the water insoluble antimicrobial agents, water soluble agents, and enzymes may be present in either the first or second oral compositions if there are two phases. These agents may be present at levels of from about 0.01% to about 1.5%, by weight of the oral composition.
  • a dentifrice composition may be a paste, gel, or any configuration or combination thereof. If a dual phase dentifrice is desired, the first and second dentifrice compositions will be physically separated in a dentifrice dispenser. It is generally preferred that the first dentifrice composition be a paste and the second dentifrice composition be a gel.
  • the dispenser may be a tube, pump, or any other container suitable for dispensing toothpaste. Dual compartment packages suitable for this purpose are described in U.S. Patent 4,528,180; U.S. Patent 4,687,663; and 4,849,213, all to Shaeffer.
  • the dispenser will deliver approximately equal amounts of each dentifrice composition through an opening.
  • the compositions may intermix once dispensed.
  • the oral formulation may be delivered from a kit containing two separate dispensers which are used to deliver two dentifrice compositions that are both used simultaneously.
  • Overall performance of the present compositions may be defined in terms of an efficacy score/stain score ratio, wherein efficacy is measured using the in vitro Plaque Glycolysis and Regrowth Model (i-PGRM), and stain is measured using the in vitro Pellicle Tea Stain Model (i-PTSM).
  • the present compositions provide an efficacy score to stain score ratio of at least 1.2, which represents a realistic improvement in that sufficient therapeutic efficacy is maintained while achieving a reduction in staining.
  • Improvement in formulation astringency is defined as greater than 50 % increase in formulation mouth feel parameters such as dry mouth, and clean mouth indices as defined in controlled consumer testing.
  • Effectiveness for control of supragingival calculus is defined by activity in prevention of plaque calcification using the Modified Plaque Growth and Mineralization assay. Antimicrobial Activity
  • the stannous ion concentration and bioavailability required for the provision of therapeutic actions may differ for different clinical actions, for example, caries vs. gingivitis.
  • it is critical to establish a minimum antimicrobial activity level, since the therapeutic activity of stannous can be compromised below this level. It is especially important to maintain efficacy in compositions wherein binding of stannous occurs, since stannous binding can easily lead to loss of antimicrobial activity.
  • the minimum efficacy provided by the stannous ion source is defined in terms of effects in producing metabolic inhibition of dental plaque bacterial biofilms, which are responsible for numerous undesirable intraoral conditions.
  • Efficacy is thus defined in terms of a noticeable and significant reduction in in situ plaque metabolism as measured using the in vitro Plaque Glycolysis and Regrowth Model (i-PGRM), developed in our laboratories.
  • the i-PGRM has been demonstrated to provide an excellent correlation to bioavailability of stannous fluoride required to produce clinical antimicrobial, antigingivitis and antiplaque activity of oral compositions containing stannous fluoride.
  • the efficacy of stannous containing compositions for gingivitis can be directly compared to a stannous-containing dentifrice formulation such as described in U.S. 5,004,597 to Majeti, et al. or to a marketed dentifrice containing stannous fluoride, Crest Gum Care.
  • the i-PGRM is a technique where plaque is grown from human saliva, and treated with agents designed to produce various levels of antimicrobial activity.
  • the purpose of this technique is to provide a simple and quick method for determining if compounds have a direct effect on the metabolic pathways that plaque microorganisms utilize for the production of toxins which adversely affect gingival health.
  • the model focuses on the production of organic acids including lactic, acetic, propionic, and butyric.
  • This method utilizes plaque grown on polished glass rods which have been dipped in saliva overnight, soy broth and sucrose for 6 hours, and saliva again overnight. The plaque mass grown on the glass rods is then treated for 1 minute with a 3:1 water to dentifrice slurry.
  • stannous fluoride and/or other stannous salts are found in the oral compositions described herein in an effective amount to provide a desired i-PGRM score.
  • the desired i-PGRM score is measured relative to non-stannous containing formulations (negative control) and to stannous-containing formulations (positive control) such as described in U.S. 5,004,597 to Majeti et al.
  • Most preferable i-PGRM scores are significantly different from placebo controls and ideally similar to those provided by conventional stannous fluoride compositions proven effective for reducing plaque and gingivitis.
  • compositions providing at least about 60%, preferably at least about 70%, and more preferably at least about 80% of an effective stannous-containing dentifrice such as shown in Example II, Comparative Example below.
  • i-PGRM Score 100% x ( Test product mean pH - Non-Stannous Control mean pH )
  • the mean pH values refer to incubation media pH's obtained following treatment and sucrose challenge.
  • the non-stannous control plaque samples produce large amounts of acid, and hence their pH's are lower than that of plaque samples treated with the positive control (stabilized stannous fluoride dentifrice as shown in Example II, Comparative Example).
  • the effectiveness of a formulation prepared from the combination of a stannous ion source and MSA will ideally be comparable to the stannous-containing control, and hence ideal i-PGRM score should approach 100%.
  • Tooth staining is a common undesirable side effect of the use of stannous fluoride compositions.
  • Improved stannous fluoride dentifrices described herein provide reduced dental stain formation resulting from more efficient stannous delivery from stannous bound to the MSA.
  • the staining of the tooth surface typically caused by stannous is measured in the clinical situation by using a stain index such as the Lobene or Meckel indices described in the literature.
  • An in vitro staining model has also been developed which provides quantitative estimates for stannous fluoride formulation staining potential which correlate well with clinical observations. Formulations can thus be tested in advance of clinical examination using these methods.
  • the in-vitro Pellicle Tea Stain Model is a technique where an in vitro plaque biomass is grown on glass rods from pooled human stimulated saliva over the course of three days.
  • the plaque biomass is treated with 3:1 water to dentifrice supernatants, where abrasive and insoluble solids have been removed via centrifugation, to determine potential dental staining levels of the various agents.
  • the purpose of this technique is to provide a simple and quick method for determining if compounds have a direct effect on the amount of dental plaque stain.
  • This method utilizes plaque grown on polished glass rods from pooled human saliva with treatments of 5 minutes each, followed by a 10 minute tea treatment.
  • the treatment regimen is repeated at lest three times before the plaque mass is digested off the rods, filtered and absorbance at 380 nm is measured. This testing is typically done with a number of replicates to minimize experimental variances, and a mean absorbance is calculated from the replicates.
  • the stain which is typically produced by effective stannous fluoride is reduced by combining the stannous fluoride with one or a mixture of the MSA's discussed above.
  • the benefit of reducing the staining caused by stannous is achieved with the present compositions without significantly compromising the efficacy of the stannous, fluoride, and MSA.
  • the amount of staining resulting from the oral compositions of the present invention is significantly lower than the amount of staining resulting from typical dentifrices containing stannous.
  • reduced as used herein means a statistically significant reduction. Therefore, reducing the staining of stannous means that the amount of stain is statistically significantly reduced compared to a stannous-containing positive control.
  • stain may be measured relative to typical oral compositions, which do not contain stannous fluoride or another antimicrobial agent which is known to stain. Therefore, the compositions may be measured relative to very little to no stain.
  • the mean absorbance values refer to digested plaque colorimetric values obtained following dentifrice treatments and tea rinsing challenge.
  • the stannous control used is typically a high staining stannous fluoride formulation such as illustrated in Example II, Comparative Example below.
  • the stannous control samples produce large amounts of tea absorption and hence increased colorimetric absorbance.
  • the i- PTSM score is a measure of the relative level of staining. The lower the score, the lower the level of staining.
  • a stannous ion source and MSA provides a reduction in staining and will ideally have a i-PTSM score of less than about 75%, preferably less than 60%, more preferably less than 50%, most preferably less than 25%.
  • a key descriptor of the improvement in stannous compositions provided herein is the ratio of efficacy of stannous in comparison to staining potential, these being key consumer concerns.
  • the effectiveness of the oral composition of the present invention will be measured by a ratio of i-PGRM score to i-PTSM score.
  • the ratio of i-PGRM score to i-PTSM score is calculated according to the formula:
  • Ratio i-PGRM score / i-PTSM score
  • the ratio developed using these methods should be at least about 1.2 for significant improvements in stannous formulation efficacy relative to tooth staining side effects.
  • the ratio is preferably above about 1.3, more preferably above about 1.5, and most preferably above about 2.0. If there is little to no stain occurring, the ratio approaches infinity, which is preferred. Binding of Stannous
  • stannous may be accomplished by in situ binding or complexation of stannous ion with the mineral surface active agent (MSA).
  • MSA mineral surface active agent
  • evidence of binding of stannous is readily observed by potentiometric detection of available ionic fluoride.
  • binding of stannous with polyphosphate MSA ligand results in exchange of fluoride from stannous fluoride and release as ionic fluoride into solution.
  • Relevant measures of stannous binding can be assessed by this technique because fluoride is the strongest ligand in the system after the MSA binding agent.
  • fluoride release is illustrative of stannous binding by the MSA under these conditions.
  • zinc ion may have a higher affinity than stannous ion for polyphosphate anion
  • the addition of zinc salt into a mixture of stannous fluoride and polyphosphate would favor the formation of zinc-polyphosphate complex and release stannous ions that will subsequently complex free fluoride.
  • the level of free fluoride ion will be lowered by the addition of zinc ion.
  • Solutions containing stannous fluoride alone and stannous fluoride plus zinc salt were prepared. To these solutions glass H polyphosphate solution were added in increments and fluoride ion monitored via fluoride ion selective electrode. The following two solutions were prepared.
  • Astringency is an additional side effect of many stannous containing compositions which is significantly improved in the present compositions comprising the MSA's in combination with stannous and a second polyvalent cation.
  • the astringency of formulations can be measured in intraoral panels, where subjects assess mouth condition before and after tooth brushing with the test formulations. In these studies, time dependent studies can be made of dentifrice effects on consumer subjective responses. In one protocol, panelists began a conditioning series by having teeth cleaned with vigorous self oral hygiene including brushing for two three minute periods, flossing and disclosing to ensure complete plaque removal. Subjects are then assigned their test product and instructed to brush with twice per day as usual. For these tests, subjects reported in the morning to a clinic prior to any oral hygiene or food or beverage consumption.
  • the provision of anticalculus benefits is another desirable aspect of the present stannous fluoride formulations.
  • Anticalculus activity can be predicted from mineral surface activity measurements and the application of plaque growth and mineralization assays.
  • the present compositions include MSA's, such as polyphosphates that bind stannous ions.
  • Preferred compositions contain MSA phosphate polymers with significant affinity for dental surfaces, which are comprised of calcium hydroxyapatites.
  • Preferred MSA's will include phosphate polymers which produce significant reductions in calcium phosphate mineralization as established in controlled mineralization assays.
  • Polyphosphates in particular linear polyphosphates with average chain lengths greater than about 4 have been found to produce superior activity and substantivity to oral surfaces compared to pyrophosphate and some other commonly used dental cleaning ingredients.
  • the increased activity and substantivity translate into significant improvements in the prevention of dental stains and supragingival calculus and in the non-abrasive removal of dental stains.
  • the polyphosphates prevent formation of supragingival calculus by essentially disrupting the mineralization process, which is the formation of hard calcium phosphate mineral deposits on tooth enamel. By binding to tooth surfaces, polyphosphates disrupt the mineral building process, because their structures do not adequately fit the developing mineral lattice, which becomes the calculus.
  • the present invention also relates to a method of treating gingivitis and plaque with reduced staining, by using the present compositions comprising a stannous ion source, a source of polyvalent metal ions other than stannous and mineral surface- active/chelating agent such as a linear polyphosphate having an average chain length of about 4 or more.
  • a source of fluoride ions is preferably included in the compositions particularly if the stannous ion source does not comprise stannous fluoride or stannous fluorophosphate.
  • methods of providing oral care compositions which have caries, gingivitis, plaque, tartar, stain, sensitivity, aesthetics, breath, mouthfeel, and cleaning benefits. The benefits of these compositions may increase over time when the composition is repeatedly used.
  • the method of treatment will include reducing the gingivitis and plaque, as measured by the i-PGRM, while reducing the staining caused by oral composition containing stannous, as measured by the i-PTSM.
  • the ratio of the i-PGRM score to i-PTSM stain model score is above about 1.2.
  • the present invention also relates to methods for reducing the incidence of calculus on dental enamel and to methods for providing desirable mouth aesthetic benefits including reduced astringency and oral surface conditioning effects.
  • the benefits of these compositions may increase over time when the composition is repeatedly used.
  • Methods of treatment include preparing an oral composition containing a stannous ion source, a source of polyvalent cation other than stannous and a mineral surface active agent (MSA) and administering the composition to the subject.
  • Administering to the subject may be defined as having the oral care composition contact the tooth surfaces of the subject by brushing with a dentifrice or rinsing with a dentifrice slurry. Administration may also be by contacting the topical oral gel, mouthrinse, denture product, mouthspray, oral tablet, lozenge, or chewing gum with the tooth surfaces.
  • the subject may be any person or animal in need of treatment or prevention of oral conditions including plaque, gingivitis, tartar, stain, and sensitivity.
  • animal is meant to include in particular household pets or other domestic animals, or animals kept in captivity.
  • a method of treatment may include a person brushing a dog's teeth with one of the dentifrice compositions.
  • Another example would include the rinsing of a cat's mouth with an oral composition for a sufficient amount of time to see a benefit.
  • Pet care products such as chews and toys may be formulated to contain the present oral compositions.
  • the composition including stannous, second cation and MSA is incorporated into a relatively supple but strong and durable material such as rawhide, ropes made from natural or synthetic fibers, and polymeric articles made from nylon, polyester or thermoplastic polyurethane.
  • the animal chews, licks or gnaws the product the incorporated active elements are released into the animal's oral cavity into a salivary medium, comparable to an effective brushing or rinsing. Examples
  • the second polyvalent cation source is incorporated in either composition.
  • These compositions may be suitably prepared by conventional methods chosen by the formulator.
  • Example II illustrates single phase dentifrice compositions incorporating stannous salt(s) as stannous ion source, a polyvalent cation source, and Glass H sodium polyphosphate or Gantrez as MSA.
  • the compositions may be prepared using conventional methodsv

Abstract

La présente invention concerne des compositions buccales contenant une source d'ions stanneux, une source de cations polyvalents et un agent tensioactif minéral, lesdites compositions faisant preuve d'une efficacité thérapeutique accrue due à la présence d'un fluorure stanneux et/ou d'un autre sel stanneux, dont notamment des effets antimicrobiens, une régulation de la mauvaise haleine ainsi que de la formation et du métabolisme de la plaque dentaire, une réduction de la gingivite, de l'évolution vers une parodontopathie, de l'hypersensibilité de la dentine et de l'apparition de caries dentaires coronaires et radiculaires. Les effets bénéfiques précités sont obtenus avec des améliorations significatives par comparaison avec les compositions classiques contenant des ions stanneux, incluant : 1) des niveaux réduits de la coloration dentaire ; 2) une astringence réduite qui, de ce fait, améliore les caractéristiques esthétiques des compositions ; 3) une réduction de la formation du tartre dentaire, et 4) un accroissement de la stabilité, de la biodisponibilité et, par conséquent, de l'efficacité de l'ion stanneux. Les agents tensioactifs minéraux sont fondamentaux pour les surfaces minérales telles que les dents et ils présentent une activité chélatrice vis-à-vis des cations polyvalents, notamment les cations stanneux (Sn+2), zinc (Zn+2), cuivre (Cu+2), aluminium (Al+3), fer (Fe+2, Fe+3), strontium (Sr+2), calcium (Ca+2), baryum (Ba+2), magnésium (Mg+2), et manganèse (Mn+2). Les agents tensioactifs minéraux préférés incluent des polymères ou des copolymères contenant du phosphate, du phosphonate, ou des groupes carboxyle. Les compositions peuvent également contenir une source d'ion fluorure et peuvent être formulées sous forme de compositions à phase unique ou à deux phases.
PCT/IB2006/053598 2006-10-02 2006-10-02 Compositions d'hygiène buccale stanneuses WO2008041055A1 (fr)

Priority Applications (9)

Application Number Priority Date Filing Date Title
CNA2006800558505A CN101511327A (zh) 2006-10-02 2006-10-02 亚锡口腔护理组合物
JP2009529784A JP2010505760A (ja) 2006-10-02 2006-10-02 第一スズ口腔ケア組成物
EP06809475A EP2068814A1 (fr) 2006-10-02 2006-10-02 Compositions d'hygiène buccale stanneuses
RU2009111321/15A RU2469700C2 (ru) 2006-10-02 2006-10-02 Композиции для ухода за полостью рта, содержащие олово (ii)
BRPI0622151-3A BRPI0622151B1 (pt) 2006-10-02 2006-10-02 Composições estanosas para tratamento oral e método de acentuação da eficácia terapêutica das ditas composições
PCT/IB2006/053598 WO2008041055A1 (fr) 2006-10-02 2006-10-02 Compositions d'hygiène buccale stanneuses
CA002663913A CA2663913A1 (fr) 2006-10-02 2006-10-02 Compositions d'hygiene buccale stanneuses
AU2006349144A AU2006349144C1 (en) 2006-10-02 2006-10-02 Stannous oral care compositions
MX2009003557A MX2009003557A (es) 2006-10-02 2006-10-02 Composicion estanosa para el cuidado bucal.

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB2006/053598 WO2008041055A1 (fr) 2006-10-02 2006-10-02 Compositions d'hygiène buccale stanneuses

Publications (1)

Publication Number Publication Date
WO2008041055A1 true WO2008041055A1 (fr) 2008-04-10

Family

ID=38066388

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2006/053598 WO2008041055A1 (fr) 2006-10-02 2006-10-02 Compositions d'hygiène buccale stanneuses

Country Status (9)

Country Link
EP (1) EP2068814A1 (fr)
JP (1) JP2010505760A (fr)
CN (1) CN101511327A (fr)
AU (1) AU2006349144C1 (fr)
BR (1) BRPI0622151B1 (fr)
CA (1) CA2663913A1 (fr)
MX (1) MX2009003557A (fr)
RU (1) RU2469700C2 (fr)
WO (1) WO2008041055A1 (fr)

Cited By (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010235557A (ja) * 2009-03-31 2010-10-21 Sunstar Inc 多価金属化合物含有口腔用組成物
JP2011051955A (ja) * 2009-09-04 2011-03-17 Lion Corp 歯磨剤組成物
WO2010138544A3 (fr) * 2009-05-26 2011-05-12 Colgate-Palmolive Company Compositions d'hygiène bucco-dentaire à teneur renforcée en zinc soluble
EP2374446A1 (fr) * 2010-04-07 2011-10-12 GABA International Holding AG Compositions de soins oraux comprenant des ions nitrate et étain(II)
JP2012509894A (ja) * 2008-11-25 2012-04-26 ザ プロクター アンド ギャンブル カンパニー 溶融シリカを有する口腔ケア組成物
WO2013007571A2 (fr) 2011-07-12 2013-01-17 Unilever N.V. Pâte dentifrice
JP2013509404A (ja) * 2009-10-29 2013-03-14 コルゲート・パーモリブ・カンパニー フッ化第一スズとクエン酸亜鉛および低レベルの水を含む歯磨き剤
WO2011094505A3 (fr) * 2010-01-29 2013-03-21 Colgate-Palmolive Company Produit d'hygiène buccale pour émail sensible
WO2011094499A3 (fr) * 2010-01-29 2013-03-28 Colgate-Palmolive Company Produit d'hygiène buccale pour émail sensible
WO2014094900A1 (fr) * 2012-12-21 2014-06-26 Gaba International Holding Ag Composition de soin buccal
WO2014100930A1 (fr) * 2012-12-24 2014-07-03 Colgate-Palmolive Company Composition pour l'hygiène buccale
US8865137B2 (en) 2009-05-26 2014-10-21 Colgate-Palmolive Company Dentifrice composition
US8932563B2 (en) 2009-05-26 2015-01-13 Colgate-Palmolive Company Higher loading zinc-containing films
WO2015094334A1 (fr) * 2013-12-20 2015-06-25 Colgate-Palmolive Company Compositions et méthodes de soin buccal
WO2015094337A1 (fr) * 2013-12-20 2015-06-25 Colgate-Palmolive Company Compositions et méthodes de soin buccal
WO2015168877A1 (fr) 2014-05-07 2015-11-12 The Procter & Gamble Company Compositions de soin bucco-dentaire
WO2015168879A1 (fr) 2014-05-07 2015-11-12 The Procter & Gamble Company Compositions de soin bucco-dentaire
WO2015171836A1 (fr) 2014-05-09 2015-11-12 The Procter & Gamble Company Compositions buccales contenant des composés stanneux
WO2015172923A1 (fr) * 2014-05-14 2015-11-19 Henkel Ag & Co. Kgaa Agents de soin et de nettoyage bucco-dentaire permettant de réduire la coloration des dents
US9354219B1 (en) 2014-12-23 2016-05-31 Colgate-Palmolive Company Detecting stannous ions
US9435745B2 (en) 2014-12-23 2016-09-06 Colgate-Palmolive Company Measuring the rate of release of metal ions
AU2013408265B2 (en) * 2013-12-20 2016-12-15 Colgate-Palmolive Company Oral care compositions and methods
US9625449B2 (en) 2014-12-23 2017-04-18 Colgate-Palmolive Company Determining the bioavailability of zinc (II) ions
WO2017172955A1 (fr) * 2016-03-29 2017-10-05 Safewhite, Inc. Colles dentaires polyélectrolytiques pour le blanchiment des dents et de composants dentaires
EP3129000A4 (fr) * 2014-04-11 2017-11-29 Premier Dental Products Company Pâte dentifrice pour la protection et la réparation de l'émail
WO2017222548A1 (fr) * 2016-06-24 2017-12-28 Colgate-Palmolive Company Composition d'hygiène bucco-dentaire
US9877929B2 (en) 2011-10-13 2018-01-30 Premier Dental Products Company Topical vitamin D and ubiquinol oral supplement compositions
US9877930B2 (en) 2012-10-12 2018-01-30 Premier Dental Products Company Topical ubiquinol oral supplement compositions with amorphous calcium phosphate
WO2018031357A1 (fr) * 2016-08-11 2018-02-15 Colgate-Palmolive Company Compositions de soins buccaux
US9913783B2 (en) 2014-05-15 2018-03-13 The Procter & Gamble Company Dentifrice compositions having optimized preservatives
US10039697B2 (en) 2014-05-15 2018-08-07 The Procter & Gamble Company Dentifrice compositions having improved fluoride ion stability or fluoride uptake
US10149806B2 (en) 2014-05-15 2018-12-11 The Procter & Gamble Company Oral care compositions containing polyethylene glycol for physical stability
US10226414B2 (en) 2014-05-15 2019-03-12 The Procter & Gamble Company Dentifrice compositions with improved fluoride stability
US10350151B2 (en) 2014-12-26 2019-07-16 Colgate-Palmolive Company Zinc phosphate complex
WO2020219323A1 (fr) * 2019-04-26 2020-10-29 The Procter & Gamble Company Réduction de coloration de dent dérivée d'antimicrobiens cationiques
US10835477B2 (en) 2014-05-15 2020-11-17 The Procter & Gamble Company Oral care compositions containing polyethylene glycol for physical stability
US11213466B2 (en) 2014-12-26 2022-01-04 Colgate-Palmolive Company Personal care compositions with zinc phosphate active
US11504312B2 (en) 2014-12-18 2022-11-22 Colgate-Palmolive Company Mouthrinse formulations
WO2023094489A1 (fr) * 2021-11-29 2023-06-01 Glaxosmithkline Consumer Healthcare (Uk) Ip Limited Composition de dentifrice non aqueuse
US11690791B2 (en) 2014-12-26 2023-07-04 Colgate-Palmolive Company Zinc phosphate complex
US11690792B2 (en) 2019-09-30 2023-07-04 The Procter & Gamble Company Oral care compositions comprising hops beta acids and metal ions
US11918681B2 (en) 2019-09-30 2024-03-05 The Procter & Gamble Company Oral care compositions comprising hops beta acid and amino acid

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112016014486B1 (pt) * 2013-12-20 2020-03-10 Colgate-Palmolive Company Composição de enxágue bucal e uso
JP5764712B1 (ja) * 2014-12-16 2015-08-19 株式会社松風 歯質再生剤
WO2017079962A1 (fr) * 2015-11-13 2017-05-18 The Procter & Gamble Company Compositions dentifrice ayant des effets bénéfiques anti-tartre et anti-bactérien
EP3541351B1 (fr) * 2016-12-21 2023-10-04 Colgate-Palmolive Company Compositions de soins buccaux
ES2877656T3 (es) * 2017-09-29 2021-11-17 3M Innovative Properties Co Composiciones acuosas de tratamiento con fluoruro para el cuidado bucal
AU2018384633B2 (en) * 2017-12-11 2021-07-01 The Procter & Gamble Company Oral care compositions comprising phosphono-phosphate and anionic group containing polymers
MX2020005972A (es) * 2017-12-11 2022-03-07 Procter & Gamble Composiciones para el cuidado bucal que comprenden polimeros que contienen grupos fosfonato y anionicos.
US11911492B2 (en) 2018-05-14 2024-02-27 The Procter & Gamble Company Oral care compositions comprising metal ions
JP2021523142A (ja) * 2018-05-14 2021-09-02 ザ プロクター アンド ギャンブル カンパニーＴｈｅ Ｐｒｏｃｔｅｒ ＆ Ｇａｍｂｌｅ Ｃｏｍｐａｎｙ 単位用量口腔ケア組成物
AU2019416034B2 (en) * 2018-12-26 2022-09-08 Colgate-Palmolive Company Methods of inducing sIgA and mucin 5B in the oral cavity

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3105798A (en) * 1958-05-29 1963-10-01 Procter & Gamble Dentifrice composition
US4335102A (en) * 1979-09-20 1982-06-15 Lion Corporation Oral composition for caries prophylaxis
US5015466A (en) * 1990-06-26 1991-05-14 The Procter & Gamble Company Anticalculus compositions using tartrate-succinates
US5017363A (en) * 1989-11-15 1991-05-21 Gillette Canada, Inc. Stabilized stannous fluoride toothpaste
WO1995007682A1 (fr) * 1993-09-16 1995-03-23 Unilever N.V. Compositions orales contenant des composes stanneux
WO2000032160A1 (fr) * 1998-11-30 2000-06-08 The Procter & Gamble Company Procedes pour reduire l'astringence des composes stanneux de compositions de dentifrice
WO2001034108A1 (fr) * 1999-11-12 2001-05-17 The Procter & Gamble Company Compositions buccales ameliorees contenant des sels d'etain
WO2002092038A2 (fr) * 2001-05-15 2002-11-21 The Procter & Gamble Company Compositions d'hygiene buccale
US20030124067A1 (en) * 2001-11-28 2003-07-03 Jiang Yue Dentifrice compositions comprising a stable low water, phase comprising polyphosphate and ionic active ingredients
WO2004054531A1 (fr) * 2002-12-13 2004-07-01 The Procter & Gamble Company Procede d'amelioration de la fluoruration et de la mineralisation des dents

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU648040B2 (en) * 1989-11-15 1994-04-14 Gillette Canada Inc. Stabilized stannous fluoride compositions for oral care

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3105798A (en) * 1958-05-29 1963-10-01 Procter & Gamble Dentifrice composition
US4335102A (en) * 1979-09-20 1982-06-15 Lion Corporation Oral composition for caries prophylaxis
US5017363A (en) * 1989-11-15 1991-05-21 Gillette Canada, Inc. Stabilized stannous fluoride toothpaste
US5015466A (en) * 1990-06-26 1991-05-14 The Procter & Gamble Company Anticalculus compositions using tartrate-succinates
WO1995007682A1 (fr) * 1993-09-16 1995-03-23 Unilever N.V. Compositions orales contenant des composes stanneux
WO2000032160A1 (fr) * 1998-11-30 2000-06-08 The Procter & Gamble Company Procedes pour reduire l'astringence des composes stanneux de compositions de dentifrice
WO2001034108A1 (fr) * 1999-11-12 2001-05-17 The Procter & Gamble Company Compositions buccales ameliorees contenant des sels d'etain
WO2002092038A2 (fr) * 2001-05-15 2002-11-21 The Procter & Gamble Company Compositions d'hygiene buccale
US20030124067A1 (en) * 2001-11-28 2003-07-03 Jiang Yue Dentifrice compositions comprising a stable low water, phase comprising polyphosphate and ionic active ingredients
WO2004054531A1 (fr) * 2002-12-13 2004-07-01 The Procter & Gamble Company Procede d'amelioration de la fluoruration et de la mineralisation des dents

Cited By (92)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012509894A (ja) * 2008-11-25 2012-04-26 ザ プロクター アンド ギャンブル カンパニー 溶融シリカを有する口腔ケア組成物
JP2012509898A (ja) * 2008-11-25 2012-04-26 ザ プロクター アンド ギャンブル カンパニー 溶融シリカを有する白化組成物
JP2010235557A (ja) * 2009-03-31 2010-10-21 Sunstar Inc 多価金属化合物含有口腔用組成物
RU2481098C1 (ru) * 2009-05-26 2013-05-10 Колгейт-Палмолив Компани Композиции для ухода за полостью рта, которые увеличивают количество растворимого цинка
US9855200B2 (en) 2009-05-26 2018-01-02 Colgate-Palmolive Company Oral care formulations that enhance amount of soluble zinc
WO2010138544A3 (fr) * 2009-05-26 2011-05-12 Colgate-Palmolive Company Compositions d'hygiène bucco-dentaire à teneur renforcée en zinc soluble
CN102448425A (zh) * 2009-05-26 2012-05-09 高露洁-棕榄公司 提高可溶锌量的口腔护理制剂
JP2012528172A (ja) * 2009-05-26 2012-11-12 コルゲート・パーモリブ・カンパニー 可溶性亜鉛の量を増加させる口腔ケア配合物
AU2010254185B2 (en) * 2009-05-26 2012-11-15 Colgate-Palmolive Company Oral care formulations that enhance amount of soluble zinc
CN104873404A (zh) * 2009-05-26 2015-09-02 高露洁-棕榄公司 提高可溶锌量的口腔护理制剂
US8932563B2 (en) 2009-05-26 2015-01-13 Colgate-Palmolive Company Higher loading zinc-containing films
US8865137B2 (en) 2009-05-26 2014-10-21 Colgate-Palmolive Company Dentifrice composition
JP2011051955A (ja) * 2009-09-04 2011-03-17 Lion Corp 歯磨剤組成物
US10682532B2 (en) 2009-10-29 2020-06-16 Colgate-Palmolive Company Low water stannous fluoride plus zinc citrate dentifrice with improved stability, rheology, and efficacy
JP2013509404A (ja) * 2009-10-29 2013-03-14 コルゲート・パーモリブ・カンパニー フッ化第一スズとクエン酸亜鉛および低レベルの水を含む歯磨き剤
US9968803B2 (en) 2009-10-29 2018-05-15 Colgate-Palmolive Company Low water stannous fluoride plus zinc citrate dentifrice with improved stability, rheology, and efficacy
US10668306B2 (en) 2009-10-29 2020-06-02 Colgate-Palmolive Company Low water stannous fluoride plus zinc citrate dentifrice with improved stability, rheology, and efficacy
US11147992B2 (en) 2009-10-29 2021-10-19 Colgate-Palmolive Company Low water stannous fluoride plus zinc citrate dentifrice with improved stability, rheology, and efficacy
US11285342B2 (en) 2009-10-29 2022-03-29 Colgate-Palmolive Company Low water stannous fluoride plus zinc citrate dentifrice with improved stability, rheology, and efficacy
WO2011094499A3 (fr) * 2010-01-29 2013-03-28 Colgate-Palmolive Company Produit d'hygiène buccale pour émail sensible
US10610707B2 (en) 2010-01-29 2020-04-07 Colgate-Palmolive Company Oral care product for sensitive enamel care
WO2011094505A3 (fr) * 2010-01-29 2013-03-21 Colgate-Palmolive Company Produit d'hygiène buccale pour émail sensible
JP2013520401A (ja) * 2010-01-29 2013-06-06 コルゲート・パーモリブ・カンパニー 敏感なエナメル質のケアのための口腔ケア製品
CN103260705A (zh) * 2010-01-29 2013-08-21 高露洁-棕榄公司 用于敏感釉质护理的口腔护理产品
EP3409324A1 (fr) * 2010-01-29 2018-12-05 Colgate-Palmolive Company Produit d'hygiène buccale pour émail sensible
JP2015166349A (ja) * 2010-01-29 2015-09-24 コルゲート・パーモリブ・カンパニーＣｏｌｇａｔｅ−Ｐａｌｍｏｌｉｖｅ Ｃｏｍｐａｎｙ 敏感なエナメル質のケアのための口腔ケア製品
WO2011124659A1 (fr) * 2010-04-07 2011-10-13 Gaba International Holding Ag Composition de soin buccal comprenant des ions stanneux et nitrate
US8926950B2 (en) 2010-04-07 2015-01-06 Gaba International Holding Ag Oral care composition comprising stannous and nitrate ions
EP2374446A1 (fr) * 2010-04-07 2011-10-12 GABA International Holding AG Compositions de soins oraux comprenant des ions nitrate et étain(II)
WO2013007571A2 (fr) 2011-07-12 2013-01-17 Unilever N.V. Pâte dentifrice
US9308158B2 (en) 2011-07-12 2016-04-12 Conopco, Inc. Toothpaste comprising calcium based abrasives
US9877929B2 (en) 2011-10-13 2018-01-30 Premier Dental Products Company Topical vitamin D and ubiquinol oral supplement compositions
US9877930B2 (en) 2012-10-12 2018-01-30 Premier Dental Products Company Topical ubiquinol oral supplement compositions with amorphous calcium phosphate
AU2012396916B2 (en) * 2012-12-21 2015-10-01 Gaba International Holding Ag Oral care composition
US10292917B2 (en) 2012-12-21 2019-05-21 Colgate-Palmolive Company Oral care composition
WO2014094900A1 (fr) * 2012-12-21 2014-06-26 Gaba International Holding Ag Composition de soin buccal
EP2934432A4 (fr) * 2012-12-24 2016-11-09 Colgate Palmolive Co Composition pour l'hygiène buccale
US10195124B2 (en) 2012-12-24 2019-02-05 Colgate-Palmolive Company Oral care composition
WO2014100930A1 (fr) * 2012-12-24 2014-07-03 Colgate-Palmolive Company Composition pour l'hygiène buccale
TWI679027B (zh) * 2013-12-20 2019-12-11 美商美國棕欖公司 口腔護理組成物及方法（四）
US20160331669A1 (en) * 2013-12-20 2016-11-17 Colgate-Palmolive Company Oral care compositions and methods
WO2015094337A1 (fr) * 2013-12-20 2015-06-25 Colgate-Palmolive Company Compositions et méthodes de soin buccal
WO2015094334A1 (fr) * 2013-12-20 2015-06-25 Colgate-Palmolive Company Compositions et méthodes de soin buccal
US9789048B2 (en) * 2013-12-20 2017-10-17 Colgate-Palmolive Company Oral care compositions and methods
US20160338938A1 (en) * 2013-12-20 2016-11-24 Colgate-Palmolive Company Oral care compositions and methods
US9931291B2 (en) * 2013-12-20 2018-04-03 Colgate-Palmolive Company Oral care compositions and methods
AU2013408263B2 (en) * 2013-12-20 2016-12-15 Colgate-Palmolive Company Oral care compositions and methods
AU2013408265B2 (en) * 2013-12-20 2016-12-15 Colgate-Palmolive Company Oral care compositions and methods
AU2013408266B2 (en) * 2013-12-20 2016-12-15 Colgate-Palmolive Company Oral care compositions and methods
EP3129000A4 (fr) * 2014-04-11 2017-11-29 Premier Dental Products Company Pâte dentifrice pour la protection et la réparation de l'émail
US10213368B2 (en) 2014-05-07 2019-02-26 The Procter & Gamble Company Oral care compositions
WO2015168877A1 (fr) 2014-05-07 2015-11-12 The Procter & Gamble Company Compositions de soin bucco-dentaire
WO2015168879A1 (fr) 2014-05-07 2015-11-12 The Procter & Gamble Company Compositions de soin bucco-dentaire
US9687427B2 (en) 2014-05-07 2017-06-27 The Procter & Gamble Company Oral care compositions
AU2014393337B2 (en) * 2014-05-07 2018-01-04 The Procter & Gamble Company Oral care compositions
WO2015171836A1 (fr) 2014-05-09 2015-11-12 The Procter & Gamble Company Compositions buccales contenant des composés stanneux
WO2015172923A1 (fr) * 2014-05-14 2015-11-19 Henkel Ag & Co. Kgaa Agents de soin et de nettoyage bucco-dentaire permettant de réduire la coloration des dents
US10039697B2 (en) 2014-05-15 2018-08-07 The Procter & Gamble Company Dentifrice compositions having improved fluoride ion stability or fluoride uptake
US10835477B2 (en) 2014-05-15 2020-11-17 The Procter & Gamble Company Oral care compositions containing polyethylene glycol for physical stability
US9913783B2 (en) 2014-05-15 2018-03-13 The Procter & Gamble Company Dentifrice compositions having optimized preservatives
US10149806B2 (en) 2014-05-15 2018-12-11 The Procter & Gamble Company Oral care compositions containing polyethylene glycol for physical stability
US10226414B2 (en) 2014-05-15 2019-03-12 The Procter & Gamble Company Dentifrice compositions with improved fluoride stability
US11504312B2 (en) 2014-12-18 2022-11-22 Colgate-Palmolive Company Mouthrinse formulations
US9354219B1 (en) 2014-12-23 2016-05-31 Colgate-Palmolive Company Detecting stannous ions
US9435745B2 (en) 2014-12-23 2016-09-06 Colgate-Palmolive Company Measuring the rate of release of metal ions
US9625449B2 (en) 2014-12-23 2017-04-18 Colgate-Palmolive Company Determining the bioavailability of zinc (II) ions
US10350151B2 (en) 2014-12-26 2019-07-16 Colgate-Palmolive Company Zinc phosphate complex
US11213466B2 (en) 2014-12-26 2022-01-04 Colgate-Palmolive Company Personal care compositions with zinc phosphate active
US11690791B2 (en) 2014-12-26 2023-07-04 Colgate-Palmolive Company Zinc phosphate complex
US11344486B2 (en) 2014-12-26 2022-05-31 Colgate-Palmolive Company Zinc phosphate complex
WO2017172955A1 (fr) * 2016-03-29 2017-10-05 Safewhite, Inc. Colles dentaires polyélectrolytiques pour le blanchiment des dents et de composants dentaires
US9937120B2 (en) 2016-03-29 2018-04-10 Safewhite, Inc. Polyelectrolyte dental adhesives for whitening teeth and teeth components
US10201491B2 (en) 2016-03-29 2019-02-12 Safewhite, Inc. Polyelectrolyte dental adhesives for whitening teeth and teeth components
AU2016410613B2 (en) * 2016-06-24 2019-08-15 Colgate-Palmolive Company An oral care composition
US11253444B2 (en) 2016-06-24 2022-02-22 Colgate-Palmolive Company Oral care composition
WO2017222548A1 (fr) * 2016-06-24 2017-12-28 Colgate-Palmolive Company Composition d'hygiène bucco-dentaire
CN109328092A (zh) * 2016-06-24 2019-02-12 高露洁-棕榄公司 口腔护理组合物
US10238896B2 (en) 2016-08-11 2019-03-26 Colgate-Palmolive Company Oral care compositions
WO2018031357A1 (fr) * 2016-08-11 2018-02-15 Colgate-Palmolive Company Compositions de soins buccaux
US10857395B2 (en) 2016-08-11 2020-12-08 Colgate-Palmolive Company Oral care compositions
AU2017311016B2 (en) * 2016-08-11 2019-10-31 Colgate-Palmolive Company Oral care compositions
US10525289B2 (en) 2016-08-11 2020-01-07 Colgate-Palmolive Company Oral care compositions
AU2020203592B2 (en) * 2016-08-11 2021-09-09 Colgate-Palmolive Company Oral care compositions
WO2020219323A1 (fr) * 2019-04-26 2020-10-29 The Procter & Gamble Company Réduction de coloration de dent dérivée d'antimicrobiens cationiques
CN113747948A (zh) * 2019-04-26 2021-12-03 宝洁公司 减少来源于阳离子抗微生物剂的牙齿变色
US11191709B2 (en) 2019-04-26 2021-12-07 The Procter & Gamble Company Reduction of tooth staining derived from cationic antimicrobials
US11826452B2 (en) 2019-04-26 2023-11-28 The Procter & Gamble Company Reduction of tooth staining derived from cationic antimicrobials
CN113747948B (zh) * 2019-04-26 2023-12-15 宝洁公司 减少来源于阳离子抗微生物剂的牙齿变色
US11690792B2 (en) 2019-09-30 2023-07-04 The Procter & Gamble Company Oral care compositions comprising hops beta acids and metal ions
US11696881B2 (en) 2019-09-30 2023-07-11 The Procter & Gamble Company Oral care compositions comprising hops beta acids and fluoride ions
US11918681B2 (en) 2019-09-30 2024-03-05 The Procter & Gamble Company Oral care compositions comprising hops beta acid and amino acid
WO2023094489A1 (fr) * 2021-11-29 2023-06-01 Glaxosmithkline Consumer Healthcare (Uk) Ip Limited Composition de dentifrice non aqueuse

Also Published As

Publication number Publication date
RU2009111321A (ru) 2010-11-10
CA2663913A1 (fr) 2008-04-10
EP2068814A1 (fr) 2009-06-17
MX2009003557A (es) 2009-04-15
AU2006349144B2 (en) 2013-06-20
AU2006349144A1 (en) 2008-04-10
BRPI0622151A2 (pt) 2014-07-08
BRPI0622151B1 (pt) 2022-06-07
JP2010505760A (ja) 2010-02-25
CN101511327A (zh) 2009-08-19
RU2469700C2 (ru) 2012-12-20
AU2006349144C1 (en) 2013-10-31

Similar Documents

Publication Publication Date Title
AU2006349144C1 (en) Stannous oral care compositions
US10376451B2 (en) Method of protecting teeth against erosion
US20070025928A1 (en) Stannous oral care compositions
EP1227788B1 (fr) Compositions orales contenant des ions d'etain
EP1227789B1 (fr) Compositions orales stanneuses a deux phases ameliorees
CA2508017C (fr) Methode de protection des dents contre l'erosion
AU2007201912B2 (en) Method of protecting teeth against erosion

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200680055850.5

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 06809475

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2006809475

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2663913

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2003/DELNP/2009

Country of ref document: IN

ENP Entry into the national phase

Ref document number: 2009529784

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2006349144

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: MX/A/2009/003557

Country of ref document: MX

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2006349144

Country of ref document: AU

Date of ref document: 20061002

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2009111321

Country of ref document: RU

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: PI0622151

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20090331