WO2013149322A1 - Prévention ou traitement d'une maladie parodontique - Google Patents

Prévention ou traitement d'une maladie parodontique Download PDF

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Publication number
WO2013149322A1
WO2013149322A1 PCT/CA2013/000314 CA2013000314W WO2013149322A1 WO 2013149322 A1 WO2013149322 A1 WO 2013149322A1 CA 2013000314 W CA2013000314 W CA 2013000314W WO 2013149322 A1 WO2013149322 A1 WO 2013149322A1
Authority
WO
WIPO (PCT)
Prior art keywords
applicator
oral cavity
cavity surface
antimicrobial composition
antimicrobial
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CA2013/000314
Other languages
English (en)
Inventor
Remigio Piergallini
Nikolaos Loupis
Shipra RASTOGI
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Klox Technologies Inc
Original Assignee
Klox Technologies Inc
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
Priority claimed from US13/437,553 external-priority patent/US20120251981A1/en
Priority to CN201380018455.XA priority Critical patent/CN104271143A/zh
Priority to US14/390,015 priority patent/US20150050620A1/en
Priority to SG11201405849YA priority patent/SG11201405849YA/en
Priority to IN8827DEN2014 priority patent/IN2014DN08827A/en
Priority to JP2015503717A priority patent/JP2015512423A/ja
Priority to RU2014144299A priority patent/RU2014144299A/ru
Priority to MX2014011924A priority patent/MX2014011924A/es
Application filed by Klox Technologies Inc filed Critical Klox Technologies Inc
Priority to EP13772214.6A priority patent/EP2833895A4/fr
Priority to KR1020147027731A priority patent/KR20140140062A/ko
Priority to CA2867507A priority patent/CA2867507A1/fr
Priority to HK15106091.8A priority patent/HK1205464A1/xx
Priority to AU2013243174A priority patent/AU2013243174B2/en
Publication of WO2013149322A1 publication Critical patent/WO2013149322A1/fr
Priority to ZA2014/07032A priority patent/ZA201407032B/en
Priority to IL234867A priority patent/IL234867A0/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C19/00—Dental auxiliary appliances
    • A61C19/06—Implements for therapeutic treatment
    • A61C19/063—Medicament applicators for teeth or gums, e.g. treatment with fluorides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C19/00—Dental auxiliary appliances
    • A61C19/06—Implements for therapeutic treatment
    • A61C19/063—Medicament applicators for teeth or gums, e.g. treatment with fluorides
    • A61C19/066—Bleaching devices; Whitening agent applicators for teeth, e.g. trays or strips
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/65—Tetracyclines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/40—Peroxides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/42—Phosphorus; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42—Amides
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics
    • 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
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/87—Application Devices; Containers; Packaging

Definitions

  • the disclosure relates generally to preventing or treating periodontal disease, specifically but not exclusively to devices and antimicrobial compositions in methods and uses for preventing or treating periodontal disease.
  • Periodontal diseases such as gingivitis and periodontitis
  • Treatments often require visits to a dental office. Therefore, a need exists for treatments that can be used on a more routine basis outside of a dental office.
  • a device and method for applying a brightening or antimicrobial composition to a tooth and/or gums for preventing or treating periodontal disease The device is portable and can be used outside of a dental office.
  • the device applies a certain frictional stress upon a tooth and/or gums. More preferably, the device applies a frictional stress value that allows mechanical displacement of a biofilm present on the surface of a tooth. Even more preferably, the device applies a frictional stress value that allows mechanical displacement of a pellicle layer present on the surface of a tooth, but does not induce damage to the tooth enamel.
  • teeth brightening and antimicrobial compositions for use in conjunction with the device. In certain embodiments, the composition of the disclosure has both teeth whitening and antimicrobial activity. Also disclosed herein are methods for preventing or treating periodontal disease, and uses of the antimicrobial composition and devices for preventing or treating periodontal disease.
  • a device comprising a reservoir fluidly connected to an applicator, the applicator having a frictional stress value sufficient to cause mechanical displacement of a biofilm present on a surface of a tooth and/or gum.
  • the applicator may comprise pores having a diameter of 0.1-1000 ⁇ , often but not always in conjunction with the above-indicated frictional stress value.
  • a brightening or antimicrobial composition may be disposed in the reservoir. In some embodiments, the brightening or antimicrobial composition is present in an amount ranging from 2-6 ml.
  • the device may comprise an activator configured to dispense the tooth brightening or antimicrobial composition from the reservoir onto an exterior surface of the applicator.
  • the exterior surface of the applicator has a surface area of up to 4-100 mm 2 .
  • the applicator comprises a sponge.
  • the applicator comprises a silicone tip.
  • the applicator comprises a sponge and the sponge may include pores of sufficient diameter and connectivity for the hydroxyapatite to be transported through the sponge onto an exterior surface of the sponge.
  • the brightening or antimicrobial composition comprises a source of peroxide.
  • the brightening or antimicrobial composition includes hydroxyapatite, such as where the hydroxyapatite has a particle size ranging from 10 to 200 nm.
  • a method for teeth brightening may comprise the steps of a) providing a brightening composition disposed within a cylindrical reservoir, the cylindrical reservoir being fluidly connected to an exterior surface of an applicator having a frictional stress value sufficient to cause mechanical displacement of a biofilm present on a surface of the tooth, or comprising pores having a diameter of 0.1-1000 ⁇ , or both, b) dispensing the brightening composition through the applicator onto the exterior surface of the applicator, and c) applying the brightening composition onto a tooth.
  • the brightening or antimicrobial composition is applied manually by rubbing the applicator onto a tooth and exerting pressure towards the tooth.
  • the disclosure relates to a method for treating or preventing periodontal disease, such as gingivitis or periodontitis.
  • the method may comprise the steps of a) providing a composition disposed within a reservoir, the reservoir being fluidly connected to an exterior surface of an applicator having a frictional stress value sufficient to cause mechanical displacement of a biofilm present on an oral cavity surface, or comprising pores having a diameter of 0.1-1000 ⁇ , or both, b) dispensing the composition through the applicator onto the exterior surface of the applicator, and c) applying the composition to the oral cavity surface.
  • the oral cavity surface is a tooth and/or gums.
  • the method for treating or preventing periodontal disease comprises applying a composition comprising peroxide such as hydrogen peroxide and/or hydroxyapatite.
  • the composition may comprise an antimicrobial agent such as an antibiotic or antiviral agent.
  • antibiotic agents that may be included in the composition include tetracycline, doxycycline, minocycline, amoxicillin and azithromycin.
  • the composition may be applied to the oral cavity surface, such as teeth and/or gums, at least once daily or at least once weekly.
  • the composition is applied to the gums and/or the tooth/gum junction.
  • a method for preventing or treating periodontal disease comprising: providing an antimicrobial composition disposed within a reservoir, the reservoir being fluidly connected to an exterior surface of an applicator having a frictional stress value sufficient to cause mechanical displacement of a biofilm present on an oral cavity surface; dispensing said antimicrobial composition through said applicator onto said exterior surface of said applicator; applying the antimicrobial composition to the oral cavity surface; and rubbing said applicator onto said oral cavity surface and exerting pressure towards said oral cavity surface.
  • rubbing said applicator onto said oral cavity surface and exerting pressure towards said oral cavity surface occurs at the same time as, before, or after applying the antimicrobial composition to the oral cavity surface.
  • the method may include a further step of applying new antimicrobial composition to the oral cavity surface following rubbing said applicator onto said oral cavity surface and exerting pressure towards said oral cavity surface.
  • the application of the antimicrobial composition may be as a flow of composition from the reservoir to the exterior surface of the reservoir. The flow may be continuous or otherwise.
  • a method for preventing or treating periodontal disease comprising: mechanically displacing a biofilm on an oral cavity surface; and applying an antimicrobial composition to the oral cavity surface.
  • applying the antimicrobial composition comprises contacting the oral cavity surface with an exterior surface of an applicator fluidly connected to a reservoir containing the antimicrobial composition.
  • mechanically displacing the biofilm comprises rubbing said oral cavity surface and exerting pressure towards said oral cavity surface with the external surface of the applicator, the external surface of the applicator having a frictional stress value sufficient to cause mechanical displacement of the biofilm on the oral cavity surface.
  • the antimicrobial composition is applied to the oral cavity surface at the same time as, before, or after mechanically displacing the biofilm on the oral cavity surface. In certain embodiments, new antimicrobial composition is applied to the oral cavity surface after displacing the biofilm.
  • the antimicrobial composition may be broken down by enzymes on the oral cavity surface or in the saliva. Therefore, providing fresh antimicrobial composition to the oral cavity surface, which may be a continuous or interrupted supply, can provide continued antimicrobial effect which may result in a faster treatment or more effective prevention of the periodontal disease.
  • the oral cavity surface is a gum surface, a tooth surface, or both gum and tooth surfaces.
  • the gum or tooth surfaces can include periodontal pockets, in which case the method can further comprise pushing the antimicrobial composition into the periodontal pockets.
  • the antimicrobial composition comprises a peroxide source which can be hydrogen peroxide or urea peroxide.
  • the antimicrobial composition includes hydroxyapatite which may have a particle size ranging from 10-200 nm.
  • the antimicrobial composition comprises an antibiotic agent which may be selected from tetracycline, doxycycline, minocycline, amoxicillin and azithromycin.
  • the antimicrobial composition may comprises one or more of: fluoride, triclosan, sodium bicarbonate, sweetening agent, detergent, chlorhexidine, cetylpyridinium, stannous fluoride and an amine fluoride.
  • the antimicrobial composition is applied to the oral cavity surface at least once daily, or at least once weekly.
  • a contact area between the exterior surface of the applicator and the oral cavity surface is about 0.25-400 mm 2 , about 4- 100 mm 2 or about 9-25 mm 2 .
  • the exterior surface of the applicator may have a frictional stress value greater than about 0.001 N/mm 2 .
  • the applicator may comprise pores having a diameter of 0.1-1000 ⁇ .
  • the exterior surface of the applicator may be made of any suitable material or have any suitable texture for mechanically removing biofilm.
  • the applicator may comprise a sponge or silicone.
  • the exterior surface of the applicator may comprise bristles.
  • an antimicrobial composition for preventing or treating periodontal disease, wherein the antimicrobial composition is disposed within a reservoir fluidly connected to an exterior surface of an applicator for dispensing the antimicrobial composition through the applicator onto the exterior surface of the applicator for applying the antimicrobial composition to the oral cavity surface, said exterior surface of the applicator having a frictional stress value sufficient to cause mechanical displacement of the biofilm when the applicator exterior surface is rubbed against the oral cavity surface and pressure is exerted towards said oral cavity surface.
  • an antimicrobial composition on an oral cavity surface with mechanical displacement of a biofilm on the oral cavity surface for preventing or treating periodontal disease.
  • an antimicrobial composition on an oral cavity surface having a disrupted biofilm thereon for preventing or treating periodontal disease.
  • an applicator for treating or preventing periodontal disease wherein the applicator has an external surface for applying an antimicrobial composition to an oral cavity surface applicator, the external surface having a frictional stress value sufficient to cause mechanical displacement or disruption of the biofilm present on the oral surface cavity.
  • the antimicrobial composition is disposed within a reservoir fluidly connected to an exterior surface of an applicator for contacting the oral cavity surface to apply the antimicrobial composition to the oral cavity surface, said applicator having a frictional stress value sufficient to cause mechanical displacement or disruption of the biofilm present on the oral surface cavity.
  • the applicator and reservoir are arranged to deliver the antimicrobial composition onto the exterior surface of the applicator at the same time as, before, or after, mechanical displacement of the biofilm, to prevent or treat periodontal disease.
  • the oral cavity surface is a gum surface, a tooth surface, or both gum and tooth surfaces.
  • the antimicrobial composition comprises a peroxide source, such as urea peroxide.
  • the antimicrobial composition includes hydroxyapatite, which may have a particle size ranging from 10-200 nm.
  • the antimicrobial composition may comprise one or more of: fluoride, triclosan, sodium bicarbonate, sweetening agent, detergent, chlorhexidine, cetylpyridinium, stannous fluoride and an amine fluoride.
  • the antimicrobial composition may comprise an antimicrobial agent which may be an antibiotic agent, for example, tetracycline, doxycycline, minocycline, amoxicillin and azithromycin, or an antiviral agent.
  • a contact area between the exterior surface of the applicator and the oral cavity surface is about 0.25-400 mm 2 , about 4-100 mm 2 or about 9-25 mm 2 .
  • the applicator may have a frictional stress value greater than about 0.001 N/mm 2 .
  • the applicator may comprise pores having a diameter of 0.1-1000 ⁇ .
  • the exterior surface of the applicator may be made of any suitable material or have any suitable texture for mechanically removing biofilm.
  • the applicator may comprise a sponge or silicone.
  • the exterior surface of the applicator may comprise bristles.
  • the antimicrobial composition comprises urea peroxide due to its ability to generate reactive oxygen species which can prevent or treat periodontal disease, and due to its lack of side effects.
  • urea peroxide is less easily enzymatically degraded compared to hydrogen peroxide, and is better tolerated by the mucosa of the oral cavity.
  • urea peroxide does not stain teeth, does not alter taste, and does not induce sensitivity, which can occur with other antimicrobial agents such as chlorhexidine.
  • Figure 1 shows a device for applying a brightening or antimicrobial composition to a tooth and/or gums.
  • Figure 2 shows a device for applying a brightening or an antimicrobial composition to a tooth and/or gums, wherein the device has an applicator comprising a sponge.
  • Figure 3 depicts the antibacterial activity of the composition in a disc diffusion assay.
  • the antibacterial activity of the composition is compared to peroxide positive controls as well as saline negative control.
  • Figure 4 depicts the inhibition of bacterial growth around the disc in the assay of Figure 3.
  • a device 10 and method for applying a brightening or antimicrobial composition to a tooth and/or gums comprise a reservoir 25 fluidly connected to an applicator 30.
  • the applicator is optimized with regard to its mechanical performance so as to induce a certain frictional stress upon a tooth and/or gums.
  • An advantageous choice of frictional stress allows effective tooth brightening or prevention or treatment of periodontal disease, such as gingivitis or periodontitis, but without damaging the enamel or another portion of the tooth or gums.
  • the frictional stress should be sufficient to mechanically displace a biofilm and/or pellicle layer (partially or completely) from the surface of a tooth and/or gums.
  • Biofilm as used herein is a substance that adheres to the surface of the tooth and/or gums or the pellicle layer, and may include additional components, for example substances excreted from bacteria.
  • a biofilm may include a sessile community of cells that may be microbioally derived and that are attached to a substrate or to each other. These adherent cells are often embedded in a matrix of extracellular polymeric substances that they have produced, and that exhibit an altered phenotype with respect to growth rate and gene transcription.
  • the device 10 places an applicator 30 in contact with the surface of a tooth and/or gums and delivers a tooth brightening or antimicrobial composition through the applicator 30 onto the surface of a tooth and/or gums.
  • the device 10 preferably has a reservoir 25 for storing the brightening or antimicrobial composition and an applicator 30 that is fluidly connected to the reservoir 25 via a feeder 42.
  • the device 10 may be portable and in the shape of a pencil, pen or liquid stick.
  • the device 10 includes more than one applicator 30 that may be removably engaged with the device 10.
  • the applicator 30 may be retractable.
  • the brightening or antimicrobial composition described herein may be housed directly within the reservoir 25 in the device 10 or may be supplied in a removable cartridge (not shown) within the reservoir 25 that may be replaced or refilled.
  • the device may also comprise a cap 45.
  • the friction or abrasion induced by the applicator 30 upon a tooth and/or gums can be defined in terms of frictional stress.
  • the frictional stress of an applicator 30 is of particular importance, as it indicates the efficiency with which the mechanical energy provided by the user is transferred to the surface of a tooth and/or gums.
  • the frictional stress can cause mechanical displacement of biofilm.
  • an applicator has a low frictional stress value, the energy supplied by the user is dissipated in other ways, for example, through the applicator itself, resulting in the applicator deforming.
  • Frictional stress values greater than 0.001 N mm " are advantageous. More preferably, the frictional stress values are from 0.001-0.01 N mm “2 , 0.01-0.1 N mm “2 , 0.1 to 0.2 N mm “2 , 0.2- 0.3 N mm “2 , 0.3-0.4 N mm “2 , 0.4-0.5 N mm “2 , 0.5-0.6 N mm “2 , 0.6-0.7 N mm “2 , 0.7-0.8 N mm “2 , 0.8-0.9 N mm “2 , or 0.9-1 N mm “2 . In certain embodiments, the frictional stress values may be from 1-1.5 N mm “2 , 1.5-2 N mm “2 , or even from 2-2.5 or 2.5-3 N mm “2 .
  • the frictional stress value of an applicator 30 may be measured using methods known in the art.
  • One example uses a Plint dual axis reciprocating rig (such as model TE75R, MRPRA RUBBER CONSULTANTS).
  • the device 10 is clamped to the load arm of the reciprocating rig and the angle of the device relative to the reference surface is adapted to maximize the contact area of an exterior surface of the applicator 30.
  • the clamping arrangement should be set to provide a consumer realistic normal force, N, on the applicator 30 of about 3 N.
  • the coefficient of friction is then measured between the applicator 30 and a reference surface that is similar to the surface of a tooth and/or gums.
  • the applicator 30 is measured wet using a brightening or antimicrobial composition as given in Example 1.
  • the coefficient of friction is measured over the central 10 mm of four traverses of 20 mm in both the forward and reverse direction at a speed of 1 mm s and an average value calculated. Measurements with the applicator 30 in final measuring position are repeated three times to check reproducibility.
  • the applicator (e.g., 30) comprises a sponge 40.
  • the sponge 40 includes pores 41 that are fluidly connected to a feeder (e.g., 42) which receives the brightening or antimicrobial composition from reservoir (e.g., 25).
  • the sponge 40 is comprised of pores 41 having a mean diameter of about 0.1-1000 ⁇ . More preferably, the pores have a mean diameter of about 0.1-100 ⁇ , 100-200 ⁇ , 200-300 ⁇ , 300-500 ⁇ , 500-750 ⁇ or 750-1000 ⁇ .
  • the sponge 40 may be made of synthetic or man-made or natural materials such as felt, foam, polyethylene, nylon, silicone, etc.
  • the sponge 40 is made of a material resistant to peroxide-induced corrosion.
  • the applicator comprises a sponge 40 made of nylon such as flocked nylon.
  • Figure 2 illustrates an exemplary embodiment in which the applicator comprises a sponge 40.
  • the sponge 40 is optimized with regard to having pores 41 of sufficient diameter and connectivity for particles (e.g., hydroxyapatite particles, as described below) in the brightening or antimicrobial composition to be transported through the pores 41 onto an exterior surface of the applicator 30.
  • BrightOne (www.blancone.it) sold by International Dental Supply includes a sponge having the above described characteristics.
  • the contact area between the exterior surface of the applicator 30 and a surface of a tooth and/or gums preferably is from 0.25-400 mm 2 , 4-100 mm 2 , or 9-25 mm 2 . Such a contact area ensures optimal mechanical removal of biofilm and allows for efficient application of the brightening or antimicrobial composition onto the surface of a tooth and/or gums.
  • Measurements of the contact area of the exterior surface of the applicator 30 can be carried out with a dry applicator 30.
  • the dry applicator 30 is wetted by pressing it against a pad containing a brightening or antimicrobial composition and then clamping the device 10 to the load arm of a plint dual axis reciprocating rig (such as model TE75R, MRPRA RUBBER CONSULTANTS).
  • a mark on a contact surface that is representative of the contact area of the exterior surface of the applicator 30 is obtained by controlled lowering and rising of the plint load arm towards and away from the reference surface.
  • the angle of the device relative to the reference surface is adapted to maximize the contact area between the applicator 30 and the reference surface.
  • the contact time should be approximately 1 s while a normal load of about 3 N should be applied on the application device.
  • the contact area can then be calculated from the mean length and width of the mark determined using a magnifying lens with a graticule. Measurements with the applicator 30 in final measuring position are repeated three times to check reproducibility.
  • the device 10 may dispense the brightening or antimicrobial composition from the reservoir 25 onto an exterior surface of the applicator 30 through the feeder 42 via capillary action, such as in a flow through pen, or by exerting pressure on the applicator 30 by pushing the device 10 onto a surface of a tooth and/or gums, or via an activator, such as a mechanical piston with a click mechanism, a twist button and ratchet mechanism, or a push button mechanism, or through a vacuum method of ejection, or through other mechanical means that transfer the composition from the reservoir 25 to an oral cavity surface in need of treatment.
  • the activator may be positioned on a first end or side wall of the device 10.
  • the device has an activator comprising a push button.
  • the push button activator With the push button activator, the user pushes the button located on a first end or side wall of the device 10, which causes the transfer of the composition from the reservoir 25 through the feeder 42 and onto the exterior surface of the applicator 30.
  • push button activator has an arrangement that allows partitioning of the brightening composition. This can be achieved, for example, via a catch arresting mechanism connected to the push button activator. From the sound of the catch upon actuating the push button activator, the user is able to recognize that a single dose of the brightening or antimicrobial composition has been dispensed onto the exterior surface of the applicator 30.
  • a user applies the composition to a tooth and/or gum surface by manually rubbing the applicator 30 onto the tooth and/or gums and exerting pressure towards the tooth and/or gums.
  • manually rubbing the applicator 30 onto the tooth and/or gums and exerting pressure towards the tooth and/or gums causes mechanical displacement of a biofilm from the tooth and/or gum surface.
  • a set of instructions can be provided to the user to describe how to apply the composition from the device 10 onto the teeth and/or gums.
  • the reservoir 25 is made of peroxide-resistant materials.
  • the reservoir 25 is made from fluoropolymers, polypropylene, polyethylene, or other such polymers that are compatible with the ingredients of the composition of the present disclosure.
  • the devices of the disclosure may be used for delivering a variety of compositions in particular to the teeth and gums.
  • the devices deliver compositions that brighten teeth and/or have antimicrobial properties.
  • the compositions described herein may be used for the treatment of periodontal disease such as gingivitis or periodontitis.
  • Compositions with antimicrobial activity may also have teeth whitening activity.
  • preventing is art-recognized, and when used in relation to a condition, such as a periodontal disease such as periodontitis, is well understood in the art, and includes administration of a composition which reduces the frequency of, or delays the onset of, symptoms of a medical condition in a subject relative to a subject which does not receive the composition.
  • prevention of periodontitis includes, for example, reducing the inflammation or infection of the ligaments and bones that support the teeth in a population of patients receiving a prophylactic treatment relative to an untreated control population.
  • prophylactic treatment is art-recognized and refers to administration of a drug to a host. If it is administered prior to clinical manifestation of the unwanted condition (e.g., disease or other unwanted state of the host animal) then the treatment is prophylactic, i.e., it protects the host against developing the unwanted condition.
  • unwanted condition e.g., disease or other unwanted state of the host animal
  • Treating" a condition or disease refers to curing as well as ameliorating at least one symptom of the condition or disease.
  • the composition used herein is comprised of a gel carrier and at least one brightening agent dispersed throughout the gel carrier.
  • the brightening agent or antimicrobial agent may be dissolved in the gel carrier or simply dispersed homogeneously in the carrier as an insoluble suspended solid particulate.
  • the composition may comprise a peroxide source.
  • Hydrogen peroxide is a powerful oxidizing agent.
  • the concentration of hydrogen peroxide in the present composition is from about 0.001 -10% by weight of the composition, such as 1 -7% or 4-6%.
  • Urea hydrogen peroxide also known as urea peroxide, carbamide peroxide or percarbamide
  • the concentration of urea peroxide in the present composition is from about 0.003-30% by weight of the composition, such as about 1-25%), 10-20%> or 13- 17%.
  • the composition may comprise a bicarbonate salt such as sodium bicarbonate.
  • the gel carrier may contain any number of ingredients that increase the viscosity of the composition and may be present in an amount ranging from about 35-95%, or 45-70%), or 55- 65% by weight of the composition. In certain embodiments, sufficient gel carrier is added to obtain a composition having a viscosity of about 10,000 to 200,000 cps, or about 30,000 to 150,000, or 50,000 to 120,000.
  • the gel carrier may comprise one or more polymers. Preferred polymers are high molecular weight polymers of acrylic acid such as Carbopol®.
  • the gel carrier may also include cellulose derivatives (such as hydroxyethyl cellulose, carboxymethyl cellulose sodium, and methyl cellulose), gums (such as sodium alginate, carrageenan, xanthan gum, tragacanth gum, acacia gum, jellan gum, and native jellan gum), synthetic binders (such as polyvinyl alcohol, carboxyvinyl polymer, polyvinyl pyrrolidone, propylene glycol and polyethylene oxide), natural polyols (such as glycerin, mannitol, sorbitol and maltitol) and inorganic binders (such as silica gel, aluminum silica gel, bee gum, and Laponite).
  • cellulose derivatives such as hydroxyethyl cellulose, carboxymethyl cellulose sodium, and methyl cellulose
  • gums such as sodium alginate, carrageenan, xanthan gum, tragacanth gum, acacia gum, jellan gum,
  • the gel carrier may contain a polymer in combination with a synthetic binder and/or a natural polyol, such as 12-18%) synthetic binder (e.g., propylene glycol), 40-50%) natural polyol (e.g., glycerin), and 0.5-4%> of polymer (e.g., Carbopol).
  • the composition comprises flavoring agents. Flavoring agents that are useful include essential oils as well as various flavoring aldehydes, esters, alcohols, and similar materials.
  • chemicals such chemicals as menthol, carvone, and anethole, and synthetic flavors like Evercool, and derivatives of cyclic alpha-keto enamines.
  • the flavoring agent is incorporated in the brightening liquid composition of the present disclosure at a concentration of about 0.05 to about 2%, or preferably about 0.1 to about 0.5% by weight of the composition.
  • a sweetening material may also be employed as a complement to the flavoring material. Suitable sweetening agents are water soluble and include sodium saccharin, sodium cyclamate, xylitol, perillartien, D-tryptophan, aspartame, dihydrochalcones and the like.
  • the composition comprises a brightening particulate.
  • the brightening particulates may comprise a form of calcium phosphate.
  • the calcium phosphate may have a structure selected from tetracalcium phosphate, amorphous calcium phosphate, alpha- tricalcium phosphate, beta-tricalcium phosphate and hydroxyapatite (Ca 5 (OH)(P0 4 ) 3 ).
  • the calcium phosphate may be a substantially aqueous insoluble calcium phosphate and noncrystalline, poorly crystalline or crystalline form such as, for example, crystalline hydroxyapatite.
  • the composition includes nanoparticles of hydroxyapatite.
  • Hydroxyapatite has a similar physical structure as tooth enamel, and thus has a strong affinity to the tooth enamel surfaces, resulting in the hydroxyapatite particulates imparting a "natural" white appearance to the enamel surface.
  • the hydroxylapatite crystals may also cause accumulation of an electrostatic charge, due to the pressure and friction exerted by the sponge, facilitating and amplifying the penetration of ions in the enamel structure.
  • a large amount of the nanoparticles of hydroxyapatite could even percolate in the enamel and facilitate a deposition of calcium and calcium phosphate ions on the enamel.
  • the hydroxyapatite may also decrease the deleterious effects of peroxides and allow remineralization of the enamel.
  • hydroxyapatite is present in the composition of the present disclosure at a concentration of about 0.5-5%, or about 1-2% by weight of the composition.
  • hydroxyapatite particles can comprise aggregates of individual hydroxyapatite particles.
  • aggregates can have a mean diameter of from about 100 nm to about 1000 nm, and comprise hydroxyapatite particles having a mean diameter of about 10 nm to about 200 nm.
  • the composition further comprises one or more of fluoride, triclosan, detergent, clorhexidine, cetylpyridinium, stannous fluoride, and an amine fluoride.
  • amine fluorides include olaflur (N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)- dihydrofluoride) and dectaflur (9-octadecenylamine-hydrofiuoride).
  • exemplary detergents include delmopinol, sodium lauryl sulfate (SLS), and cocoamidopropyl betaine (CAPB).
  • the composition further comprises an antimicrobial agent.
  • the antimicrobial agent may be selected from an antiviral agent or an antibiotic agent.
  • Antibiotics include, for example, vancomycin, penicillin, amoxicillin, ampicillin, cefotaxime, ceftriaxone, cefixime, rifampinmetronidazole, doxycycline, tetracycline, minocycline, azithromycin, tacrolimus, cyclosporine, sirolimus, everolimus, ascomycin, erythromycin, clarithromycin, clindamycin, lincomycin, dirithromycin, josamycin, spiramycin, diacetyl-midecamycin, tylosin, roxithromycin, ABT-773, telithromycin, leucomycins, lincosamide, dactinomycin, daunorubicin, doxorubicin, idarubicin, anthracyclines, mito
  • the composition comprises a stabilizing agent.
  • the stabilizing agent utilized in the aqueous gel is present in an amount ranging from about 0.01% to about 5% by weight of the aqueous gel. An amount of approximately 1% stabilizing agent is preferred.
  • the stabilizing agent is typically selected from aminocarboxylic acids and salts thereof. Preferred stabilizers are selected from aminocarboxylic acids and alkali and/or alkali earth metal salts thereof.
  • Suitable aminocarboxylic acids include trans- 1 ,2-cyclohexylene dinitrilotetraacetic acid (CDTA), ethyl enediamine tetraacetic acid (EDTA), N-(2- hydroxyethyl) ethylenediamine triacetic acid (HEDTA), Nitrilotriacetic acid (NTA), diethylene triamine pentaacetic acid (DTP A), triethylene tetraamine hexaacetic acid (TTHA), and ethyleneglycol bis (2-aminoethylether) tetraacetic acid (GEDTA).
  • CDTA trans- 1 ,2-cyclohexylene dinitrilotetraacetic acid
  • EDTA ethyl enediamine tetraacetic acid
  • HEDTA N-(2- hydroxyethyl) ethylenediamine triacetic acid
  • NTA Nitrilotriacetic acid
  • DTP A diethylene triamine pentaacetic acid
  • a neutralizing agent may be added to the composition.
  • the inorganic and organic neutralizing agents which may be employed are bases. Suitable bases include alkali metal hydroxides and ammonium hydroxide, carbonates, alkoxides, oxides, peroxides, superoxides, and water soluble organic amines. Amino acids such as ⁇ -alanine and lysine can also be used for neutralization and viscosity modification.
  • Preferred bases include sodium hydroxide, potassium hydroxide, ammonium hydroxide, triethanolamine (TEA), aminomethyl propanol (AMP), 2-amino-2-hydroxymethyl-l ,3- propanediol (Tromethamine), tetrahydroxypropyl ethyl enediamine, and tris(hydroxymethyl)aminomethane (TRIS).
  • the neutralizing agent will be used to obtain a brightening composition having a pH of about 4 to 10, or about 5 to 7, or about 5.5 to 6.5.
  • An exemplary composition was prepared by mixing the following components.
  • Nutrient medium was inoculated with fresh bacteria from the gum-teeth junction and cultured at 37°C with agitation. 24h later 500 ih of bacterial suspension were spread onto agar petri dishes, and sterile nylon discs of 8mm were placed on the plates. 15 ⁇ ⁇ of test solutions (saline, 1% H 0 2 and 4.3% H 2 0 2 ) or 500 ⁇ of the composition of Example 1 were applied on the disc, and the plates were incubated at 37°C for 24h. As shown in Figures 3 and 4, the composition of Example 1 displays a clear bactericidal activity on bacteria from gum- teeth junction as illustrated by the diameter of bacteria-free zone around the disc.

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Abstract

La présente invention concerne un procédé pour traiter ou prévenir une maladie parodontique, telle que la gingivite ou la parodontite. Le procédé peut comprendre la fourniture d'une composition antimicrobienne disposée dans un réservoir, le réservoir étant en communication fluidique avec une surface extérieure d'un applicateur ayant une valeur de contrainte de frottement suffisante pour causer le déplacement mécanique d'un biofilm présent sur une surface de cavité orale ; la distribution de ladite composition antimicrobienne par l'intermédiaire dudit applicateur sur ladite surface extérieure dudit applicateur ; l'application de la composition antimicrobienne sur la surface de cavité orale ; et le frottement dudit applicateur sur ladite surface de cavité orale et l'application d'une pression sur ladite surface de cavité orale.
PCT/CA2013/000314 2012-04-02 2013-04-02 Prévention ou traitement d'une maladie parodontique Ceased WO2013149322A1 (fr)

Priority Applications (14)

Application Number Priority Date Filing Date Title
AU2013243174A AU2013243174B2 (en) 2012-04-02 2013-04-02 Preventing or treating periodontal disease
EP13772214.6A EP2833895A4 (fr) 2012-04-02 2013-04-02 Prévention ou traitement d'une maladie parodontique
SG11201405849YA SG11201405849YA (en) 2012-04-02 2013-04-02 Preventing or treating periodontal disease
IN8827DEN2014 IN2014DN08827A (fr) 2012-04-02 2013-04-02
JP2015503717A JP2015512423A (ja) 2012-04-02 2013-04-02 歯周病の予防または治療
RU2014144299A RU2014144299A (ru) 2012-04-02 2013-04-02 Предупреждение или лечение заболевания пародонта
MX2014011924A MX2014011924A (es) 2012-04-02 2013-04-02 Prevencion o tratamiento de la enfermedad periodontal.
CN201380018455.XA CN104271143A (zh) 2012-04-02 2013-04-02 牙周病的预防或治疗
KR1020147027731A KR20140140062A (ko) 2012-04-02 2013-04-02 치주 질환 예방 또는 치료
CA2867507A CA2867507A1 (fr) 2012-04-02 2013-04-02 Prevention ou traitement d'une maladie parodontique
US14/390,015 US20150050620A1 (en) 2012-04-02 2013-04-02 Preventing or treating periodontal disease
HK15106091.8A HK1205464A1 (en) 2012-04-02 2013-04-02 Preventing or treating periodontal disease
ZA2014/07032A ZA201407032B (en) 2013-04-02 2014-09-26 Preventing or treating periodontal disease
IL234867A IL234867A0 (en) 2012-04-02 2014-09-29 Prevention and treatment of disease related to the tooth bearing

Applications Claiming Priority (2)

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US13/437,553 US20120251981A1 (en) 2011-03-22 2012-04-02 Device and method for administering teeth whitening and antimicrobial compositions
US13/437,553 2012-04-02

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CA (1) CA2867507A1 (fr)
HK (1) HK1205464A1 (fr)
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3544667A4 (fr) * 2016-11-28 2020-12-02 Therma Bright Inc. Dispositifs pour appliquer un traitement topique
US11992640B2 (en) 2016-11-28 2024-05-28 The Jenex Corporation Devices for applying a topical treatment

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7208613B2 (ja) * 2018-08-29 2023-01-19 リジェンティス株式会社 歯の漂白用のデバイス及びキット
JP2023503060A (ja) * 2019-11-27 2023-01-26 ザ プロクター アンド ギャンブル カンパニー 投薬インジケータ
CA3277885A1 (fr) * 2022-12-21 2024-07-11 Cutting Edge Technology. Llc Formulation pharmaceutique

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5829976A (en) * 1996-04-12 1998-11-03 Green; Warren F. Medicament-containing interproximal dental brush
US20080274066A1 (en) * 2003-07-28 2008-11-06 Britesmile Professional, Inc. Compositions, Methods, Devices, and Kits for Maintaining or Enhancing Tooth Whitening
US20090269121A1 (en) * 2008-04-23 2009-10-29 Unicep Packaging, Inc. Dispensing and applicator devices

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5611687A (en) * 1995-11-06 1997-03-18 Dental Concepts Inc. Oral hygiene delivery system
CN2250124Y (zh) * 1995-11-24 1997-03-26 杨上闰 一种用于擦除牙齿色斑的笔
JPH115722A (ja) * 1997-06-13 1999-01-12 Hideki Aoki 口腔内洗浄用水性組成物
JP4199333B2 (ja) * 1998-08-07 2008-12-17 宇部マテリアルズ株式会社 歯磨組成物
JP3836456B2 (ja) * 2003-08-08 2006-10-25 株式会社ジーシー １ペースト形態の歯牙用漂白材
WO2005037127A1 (fr) * 2003-10-14 2005-04-28 Colgate-Palmolive Company Applicateur et methode d'application d'une composition de blanchiment des dents
US20060142411A1 (en) * 2004-12-29 2006-06-29 Sayed Ibrahim Instant tooth whitening with silicone resin and silicone adhesive
US20060280700A1 (en) * 2005-06-08 2006-12-14 Isler Stuart L Oral hygiene system to fight the effects of aging on the mouth, gums, and teeth
FR2909844B1 (fr) * 2006-12-14 2009-09-11 Oreal Stylo a pointe feutre pour le maquillage des ongles

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5829976A (en) * 1996-04-12 1998-11-03 Green; Warren F. Medicament-containing interproximal dental brush
US20080274066A1 (en) * 2003-07-28 2008-11-06 Britesmile Professional, Inc. Compositions, Methods, Devices, and Kits for Maintaining or Enhancing Tooth Whitening
US20090269121A1 (en) * 2008-04-23 2009-10-29 Unicep Packaging, Inc. Dispensing and applicator devices

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP2833895A4 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3544667A4 (fr) * 2016-11-28 2020-12-02 Therma Bright Inc. Dispositifs pour appliquer un traitement topique
US11344707B2 (en) 2016-11-28 2022-05-31 Therma Bright Inc. Devices for applying a topical treatment
US11992640B2 (en) 2016-11-28 2024-05-28 The Jenex Corporation Devices for applying a topical treatment

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EP2833895A1 (fr) 2015-02-11
IN2014DN08827A (fr) 2015-05-22
EP2833895A4 (fr) 2016-03-02
CN104271143A (zh) 2015-01-07
MX2014011924A (es) 2015-05-11
SG11201405849YA (en) 2014-10-30
KR20140140062A (ko) 2014-12-08
RU2014144299A (ru) 2016-05-27
IL234867A0 (en) 2014-12-31
JP2015512423A (ja) 2015-04-27
CA2867507A1 (fr) 2013-10-10
AU2013243174B2 (en) 2018-01-25
AU2013243174A1 (en) 2014-10-09
HK1205464A1 (en) 2015-12-18

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