WO2015157679A1 - Gels de brossage pour la protection et la réparation de l'émail - Google Patents

Gels de brossage pour la protection et la réparation de l'émail Download PDF

Info

Publication number
WO2015157679A1
WO2015157679A1 PCT/US2015/025385 US2015025385W WO2015157679A1 WO 2015157679 A1 WO2015157679 A1 WO 2015157679A1 US 2015025385 W US2015025385 W US 2015025385W WO 2015157679 A1 WO2015157679 A1 WO 2015157679A1
Authority
WO
WIPO (PCT)
Prior art keywords
fluoride
enamel
calcium
brushing
substantivity
Prior art date
Application number
PCT/US2015/025385
Other languages
English (en)
Inventor
William A. Mchale
Dale G. Brown
Original Assignee
Premier Dental Products 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
Priority claimed from US14/251,149 external-priority patent/US9586064B2/en
Application filed by Premier Dental Products Company filed Critical Premier Dental Products Company
Publication of WO2015157679A1 publication Critical patent/WO2015157679A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/90—Block copolymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/042—Gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—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
    • 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
    • A61K8/72—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
    • 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
    • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/30—Characterized by the absence of a particular group of ingredients
    • A61K2800/31—Anhydrous

Definitions

  • the present invention is directed to advances in enamel protectant and enamel repair, aqueous-free, stannous fluoride, brushing gels; whereby the protectant and repair ingredients are substantive to enamel surfaces, thereby extending the protecting and repairing processes with improved stannous fluoride effectiveness.
  • Key protectant and repair combinations for the brushing gels of the present invention comprise: stannous fluoride and calcium in aqueous-free, substantivity agents.
  • Dentifrices Dentifrices containing 850 to 1 ,150 ppm theoretical total fluorine in a gel or paste dosage form.
  • Preventive treatment gel Stannous fluoride 0.4% in an anhydrous glycerin gel, made from anhydrous glycerin and the addition of suitable thickening agents to adjust viscosity.
  • Fluoride dentifrices have been shown in numerous clinical trials to be effective anticaries agents [Stookey, J. Dent. Res. 1 990, 69(Special Issue): 805-81 2] and have been recognized as a major cause of the remarkable decline in caries prevalence in many developed countries. Dentifrices have been widely adopted around the world as the principle means of delivering topical fluoride and obtaining caries preventive benefits.
  • the current market for fluoride brushing products includes: professional and consumer oral care fluoride treatments, both OTC and Rx brushing products; including: toothpastes, gels, pastes and varnishes.
  • Rx fluoride toothpastes and Rx fluoride brushing gels are well outside fluoride Monograph levels containing up to 5000 ppm fluoride.
  • Professional oral care, in-chair, fluoride varnishes contain up to about 22,000 ppm fluoride
  • OTC fluoride toothpastes can contain up to 1 150 ppm total theoretical fluorine, the maximum level provided for by the Monograph.
  • ADA American Dental Association
  • FDA Food & Drug Administration
  • oral care professionals including: general practitioners, periodontists, orthodontists, pediatric dentists, etc. as a group; are generally concerned over the trend of increasing fluoride levels.
  • These organizations and oral care professionals generally favor using lower levels of fluoride in various in-chair treatments and various OTC and Rx, oral care, topical, home treatments for patients, provided.... enamel protection and repair, achieved with lower fluoride levels, are comparable to the results reported for brushing products with higher levels of fluoride.
  • This preference for lower fluoride-brushing products is driven by the concern over toxicity, fluorosis in children, etc., associated with exposure to high fluoride levels, long term.
  • Fluoride varnishes are generally applied professionally, at a frequency of about once every six months with the target audience comprising primarily children.
  • EPF enamel protectant factor
  • ERF enamel repair factor
  • Aqueous-free is defined as: substantially free from water.
  • Enamel Protectant Factor is defined as: the percent reduction in enamel solubility divided by the fluoride level in parts per million using FDA method #40.
  • Enamel Repair Factor is defined as: the average increase in enamel fluoride concentration divided by the fluoride level of the fluoride brushing product tested using FDA method #33.
  • “Brushing gel” is defined as: a non-abrasive fluid for administration of stannous fluoride to enamel surfaces.
  • “Mucoadhesive” is defined as: a substance that is retained for a period of time onto surfaces in the mouth that is not easily removed by the mechanical action of the tongue nor by flow of saliva.
  • Stable stannous fluoride is defined as: compositions that, when chemically assayed, substantially retains the level of stannous and/or fluoride in an unreacted state.
  • Biofilm is defined as: a surface adherent film comprised of bacteria , exuded polysaccharides, etc., that is not easily removed by mechanical means or saliva flow.
  • Substantivity agent is defined as: a composition that improves the mucosal retention of the desired agents.
  • “Cation bridging” is defined as: electrical attraction between two films or membranes initiated by cation moieties.
  • “Shift in calcium binding from bidentate to monodentate” is defined as: the loss of "chelate”-like binding by calcium cations with a corresponding increase in single ligand binding by calcium cations.
  • “Liquid nonionic surfactant” is defined as: a liquid composition that indicates surface active properties with the absence of charged species.
  • Solid nonionic surfactant is defined as: a solid composition that indicates surface active properties with the absence of charged species.
  • CaF + moiety is defined as: a monodentate calcium fluoride ion.
  • Linear, polymeric, polycarboxylar.es, substantivity enhancer is defined as: a linear polymer with carboxylate substituents that increases retention of compositions onto charged surfaces.
  • Embodision discontinuous phase is defined as: the minor component in an emulsion that is surrounded by a continuous phase.
  • Emsion continuous phase is defined as: an emulsion component that surrounds discontinuous phase component.
  • the present invention is directed to aqueous-free, brushing gel compositions, wherein the brushing gels contain stannous fluoride and calcium in an aqueous-free, substantivity agent.
  • the brushing gels of the present invention protect and repair enamel more effectively than brushing gels and toothpaste compositions containing comparable or substantially higher levels of fluoride, as indicated by comparative EPF and ERF values reported herein.
  • the enamel protectant and enamel repair, brushing gel compositions of the present invention when brushed onto enamel, form substantive, mucoadhesive gels in the presence of saliva; which mucoadhesive gels gradually release stable stannous fluoride and calcium onto enamel. This slow release continues until the mucoadhesive gel is eventually totally solubilized by saliva. This gradual release minimizes the "wash-out" effect traditionally experienced with fluoride brushing products.
  • the resultant enamel protectant and enamel repair increases in EPF and ERF values, resulting from the extended enamel residence time of stannous fluoride, calcium and cation bridging associated with microbial fluoride binding to biofilm. This improved stannous fluoride efficiency reduces the need to resort to elevated fluoride levels.
  • FIG. 1 of the Drawings summarizes comparative, in vitro, enamel protectant factor (EPF) values for enamel treated with a brushing gel of the present invention with stannous fluoride at 970 ppm fluoride, as described in Example 1 ; compared with : (a) an Rx 5000 ppm, sodium fluoride toothpaste, and (b) an OTC, 1 100 ppm, stannous fluoride toothpaste.
  • the 3.7 EPF value is for a test gel, stannous fluoride at 970 ppm fluoride.
  • the 2.2 EPF value is for Crest® PRO-HEALTH®, stannous fluoride at 1 100 ppm fluoride.
  • the 0.1 EPF value is for Clinpro® 5000, sodium fluoride at 5000 ppm fluoride.
  • FIGs 2 and 3 of the Drawings illustrate enamel repair factor (ERF) values for brushing gels of the present invention with compositions, as described in Examples 1 and 2; with stannous fluoride at 970 ppm compared with toothpastes having stannous fluoride at 1 100 ppm and sodium fluoride at 900 ppm or sodium fluoride at 5000 ppm, respectively.
  • the 300 ERF value is for a test gel, stannous fluoride at 970 ppm fluoride; the 170 ERF value is for Crest® PRO-HEALTH®, stannous fluoride at 1 100 ppm fluoride; and the 65 ERF value is for Clinpro® 5000, sodium fluoride at 5000 ppm fluoride.
  • the 270 ERF value is for a test gel, stannous fluoride at 970 ppm fluoride; and the 140 ERF value is for Crest® PRO-HEALTH®, stannous fluoride at 1 1 00 ppm fluoride.
  • Figures 4 through 6 present ERF values for brushing gels of the present invention comprising compositions, as described in Examples 3 through 5.
  • the 380 ERF value is for a test gel, stannous fluoride at 970 ppm fluoride; and the 21 0 ERF value is for Crest® PRO-HEALTH®, stannous fluoride at 1 100 ppm fluoride.
  • the 410 ERF value is for a test gel, stannous fluoride at 970 ppm fluoride; and the 21 0 ERF value is for Crest® PRO-HEALTH®, stannous fluoride at 1 100 ppm fluoride.
  • Fig. 4 the 380 ERF value is for a test gel, stannous fluoride at 970 ppm fluoride; and the 21 0 ERF value is for Crest® PRO-HEALTH®, stannous fluoride at 1 100 ppm fluoride.
  • the 21 0 ERF value is for Crest® PRO-HEALTH®, stan
  • the ERF value of 1070 is for a test gel, stannous fluoride at 970 ppm fluoride; and the ERF value of 210 is for Crest® PRO-HEALTH®, stannous fluoride at 1 1 00 ppm fluoride.
  • Aqueous-free, stannous fluoride, calcium, brushing gels of the present invention comprise substantivity agents that contain various enamel protectant and enamel repair ingredients. These substantivity agents function as carriers for various enamel protectant and repair ingredients. These substantivity agents are characterized by their ability, in the presence of saliva, to form mucoadhesive gels which are substantive to enamel with biofilm. These substantive, mucoadhesive gels are further characterized by their ability to: (a) gradually dissolve when exposed to saliva flow, and (b) gradually release various enamel protectant and enamel repair ingredients, in an unreacted state, onto enamel surfaces with biofilm as they dissolve.
  • the substantivity agents of the present invention extend the duration of enamel protectant and enamel repair treatments, and support cation bridging associated with microbial fluoride binding; thereby enhancing the EPF and ERF values of various brushing gels of the present invention, while simultaneously reducing the level of fluoride required to achieve the unexpected increases in EPF and ERF values.
  • phosphate components are also included in the brushing gels. These are described by Ming Tung in U.S. Patents: 5,037,639; 5,268,167; 5,427,768; 5,437,857; 5,460,803; 5,562,895; by Tung in the American Dental Association Foundation publication, "ACP Technology,"; by Schemehorn, et. al., in The Journal of Clinical Dentistry Vol. XXII : No 2. 51 -54, 201 1 ; by the 19 references cited by Schemehorn, et. al. ; and by the description of various Gantrez® resins containing calcium, including Gantrez® MS-955 available from International Specialty Products, Wayne, NJ, USA.
  • the aqueous-free, substantivity agents of the present invention hold the various enamel protectant and enamel repair ingredients, including stannous fluoride, calcium and phosphate components, in a condition where these ingredients remain stable and unreacted.
  • this aqueous-free, substantivity agent When this aqueous-free, substantivity agent is exposed to saliva, it forms a mucoadhesive gel that is substantive to enamel with biofilm. This mucoadhesive gel continues to hold the enamel protectant and enamel repair ingredients onto enamel surfaces with biofilm without the ingredients reacting. These ingredients eventually react upon being released onto saliva- and biofilm-coated, enamel surfaces.
  • this mucoadhesive, substantivity agent is totally dissolved by saliva, releasing the balance of unreacted enamel protectant and enamel repair ingredients onto saliva- and biofilm-coated, enamel surfaces.
  • Aqueous-free, brushing gels of the present invention contain enamel protectant and enamel repair ingredients, suitable for protecting and repairing dental enamel ; wherein :
  • the enamel protectant and enamel repair ingredients contained in the substantivity agents are gradually released onto the enamel in an unreacted state as the saliva soluble, substantivity agent undergoes saliva dissolution at rates, which are controlled by saliva flow and the composition of the substantivity agent;
  • saliva soluble, aqueous-free emulsions used as substantivity agents include those emulsions that are comprised of polydimethylsiloxane polymers in solid nonionic surfactants, as described in U.S. Patents: 5,032,387; 5,098,71 1 ; 5,538,667; 5,651 ,959; having the structural formula:
  • liquid having the structural formula:
  • liquid, nonionic surfactants comprise the continuous phase of the aqueous-free emulsions.
  • These liquid, nonionic surfactants are selected from the group consisting of: poloxamer, having the structural formula set out above, as well as mixtures of such liquid, nonionic surfactants with solid, nonionic surfactants; wherein the mixture is liquid, including: solid, nonionic surfactants having the structural formula set out above.
  • aqueous-free, saliva soluble emulsions for use as substantivity agents of the present invention include aqueous-free emulsions comprising a liquid, nonionic, continuous phase and a discontinuous phase of polydimethylsiloxane (PDMS) at viscosities ranging from between about 1500 cs and about 2.5 million cs.
  • aqueous-free emulsions include a liquid, nonionic, surfactant, continuous phase and a discontinuous phase PDMS at viscosities between about 10,000 cs and 2.5 million cs.
  • Solid surfactants useful as adjuncts to liquid, nonionic, surfactant, continuous phase are described in detail in U.S. 5,651 ,959. These liquid and liquid/solid, nonionic, surfactant emulsion mixtures are liquid and form mucoadhesive gels in the presence of saliva.
  • Preferred polydimethylsiloxanes are selected from the group consisting of polydimethylsiloxane: at 1 500 cs, at 1 0,000 cs, at 100,000 cs, at 250,000 cs, at 500,000 cs, at 750,000 cs, at 1 .5 million cs, at 2.2 million cs, at 2.5 million cs and combinations thereof.
  • Foam modulators are useful in the present invention. These include, without limitation: materials operable to control amount, thickness or stability of foam generated by the brushing gel composition upon agitation. Any orally acceptable foam modulator can be used, including polyethylene glycols (PEGs), also known as polyoxyethylenes. High molecular weight PEGs are suitable, including those having an average molecular weight of about 200,000 to about 7,000,000, for example about 500,000 to about 5,000,000 or about 1 ,000,000 to about 2,500,000. One or more PEGs are optionally present in a total amount of about 0.1 % to about 1 0%, for example about 0.2% to about 5% or about 0.25% to about 2%.
  • PEGs polyethylene glycols
  • High molecular weight PEGs are suitable, including those having an average molecular weight of about 200,000 to about 7,000,000, for example about 500,000 to about 5,000,000 or about 1 ,000,000 to about 2,500,000.
  • One or more PEGs are optionally present in a total amount of about 0.1 % to about 1 0%,
  • Humectants useful for the brushing gels of the present invention include, without limitation: polyhydric alcohols such as glycerin, sorbitol, xylitol or low molecular weight PEGs.
  • humectants can prevent hardening of the brushing gels upon exposure to air.
  • humectants also function as sweeteners.
  • compositions may be added to the compositions, including, for example, additional: mouth-feel agents, pH modifying agents, flavorants, sweeteners, antimicrobial (e.g., antibacterial) agents such as those described in U.S. Pat. No. 5,776,435, saliva stimulants, anti-inflammatory agents, nutrients, vitamins, proteins, antioxidants, colorants, etc. invention contain stannous fluoride at a level of 970 ppm, compared with : (a) a 900ppm sodium fluoride toothpaste, and (b) an 1 1 00 ppm stannous fluoride toothpaste or (c) a 5000 ppm sodium fluoride toothpaste.
  • Tables 2 through 1 0 summarize: (a) EPF or ERF data for brushing gels of the invention at varying compositions, as described in Examples 1 through 5, compared with commercial, fluoride, brushing products;
  • the brushing gels of the present invention contain ingredients that substantially effect enamel protection factor (EPF) and enamel repair factor (ERF) values based on bidentate binding of calcium shifting to monodentate binding of calcium in the presence of stannous fluoride.
  • EPF enamel protection factor
  • EMF enamel repair factor
  • Substantivity agents and substantivity enhancers including mixed sodium and calcium salt copolymers of methyl/vinyl/ether/maleic acid; wherein the stannous fluoride, calcium and phosphate components remain unreacted and the pH of the brushing gel when administered to saliva coated enamel is at least about 3.
  • the amount of stannous fluoride in the brushing gels of the present invention, applied to the toothbrush (dose) is not as important as the concentration of available stannous fluoride in the brushing gel.
  • reducing fluoride concentration in brushing products has been reported not to be as effective as regular concentration fluoride products.
  • the extraordinary EPF and ERF values of the brushing gels of the present invention allow for reducing stannous fluoride concentrations while effecting acceptable fluoride protection and uptake results.
  • the fluoride dose is important in regard to enamel fluorosis in children under six years of age, due to fluoride brushing gel ingestion. For this reason, reducing the amount of stannous fluoride applied with the brushing gel of the present invention is a preferred strategy over lowering the dose of stannous fluoride brushing gels of the invention intended for use by children under six years of age.
  • Stannous fluoride brushing gels of the present invention with their improved efficacy can be used at reduced stannous fluoride levels, and thereby substantially lower the risk of overdosing and the onset of fluorosis, while delivering effective EPF and ERF results.
  • plaque has the potential to remineralize even at pH values typically regarded as demineralizing.
  • stannous fluoride mouthrinses The ability of the tin ions to inhibit plaque formation has been studied primarily using stannous fluoride mouthrinses. Daily rinsing with a 0.1 percent stannous fluoride solution significantly reduces bacterial accumulation on the teeth.
  • stannous ions The action of stannous ions is mediated through their ability to bind to lipotechoic acid on the surface of Gram-positive bacterial. The surface net charge of the organisms is therefore reversed and the adsorption of the cells onto teeth is consequently reduced. Furthermore, the effectiveness of stannous fluoride solution in reducing bacterial adhesion is related to the stability of the stannous ions in aqueous solution and the rate at which they are taken up and retained by specific bacteria. The accumulation of tin in bacteria may alter their metabolism and other physiochemical characteristics.
  • the aims of the present work are to determine the rates of growth and dissolution of pure calcium fluoride in aqueous suspensions and possible mechanisms controlling these processes, and to study the properties of the calcium fluoride-like material formed by adding fluoride to systems containing hydroxyapatite crystals and/or dissolved calcium and phosphate, simulating the type of calcium fluoride-like material formed on dental enamel as a result of topical treatment with acidified solutions of high fluoride content.”
  • “From our results of dissolution of pure CaF 2 in systems containing phosphate it can be seen that 1 ⁇ phosphate has a dramatic effect on the rate of dissolution of CaF 2 .”
  • the calcium fluoride-like materials containing phosphate appear to be more likely candidates to serve as slow fluoride release agents.”
  • CaF 2 or a CaF 2 -like material/phosphate-contaminated CaF 2 is a major reaction product during topical treatment of dental hard tissues. Recently, evidence has suggested that CaF 2 is formed not only on surfaces but also to some extent in the enamel. The minimum concentration of fluoride required for CaF 2 formation is not well known and may depend on whether calcium is available from plaque fluid or only through dissolution of the dental hard tissue. Furthermore surface adsorption of fluoride to crystals may cause local concentrations necessary for CaF 2 formation. It has been suggested that CaF 2 acts as a pH-controlled reservoir of fluoride. The rate-controlling factor appears to be phosphate, which controls the dissolution rate of CaF 2 at high pH.
  • CaF 2 is the major or probably the only reaction product on dental hard tissues from short treatments with relatively concentrated fluoride agents (Cruz et. al., Scand. J. Dent. Res., 1992; 100:154-158). Without doubt, this pH-controlled depot of CaF 2 plays a major role in the cariostatic effect of topical fluoride. CaF 2 has been detected on dental hard tissues weeks and months after a single topical fluoride treatment (Caries Res., 1991 , 25:21 -26) and is the only logical way to explain that such treatments have a cariostatic effect. By treating enamel samples subjected to topical fluoride treatment with KOH, the cariostatic effect is lost (0gaard, et al., J. Dent. Res., 1990, 69:1505- 1507).”
  • hydroxyapatite In the presence of low concentrations of fluoride in solution (such as saliva or plaque fluid), hydroxyapatite might be dissolved below the critical pH (for hydroxyapatite), but the released mineral ions could be reprecipitated as fluoroapatite or a mixed fluor- hydroxyapatite. This mechanism prevents the loss of mineral ions, while providing additional protection to mineral crystallites by laying fluoride-rich other layers onto the apatite crystallites.”
  • substantivity agent refers to a composition or combination of compositions that, when administered to oral cavity surfaces with biofilm, enhance the retention of stannous fluoride and calcium to said oral cavity surfaces.
  • the unexpected enamel protectant and enamel repair features of the aqueous-free, brushing gels of the present invention are attributed to the unique substantivity properties indicated by the brushing gels of the invention.
  • preferred substantivity agents for the brushing gels of the present invention include various aqueous-free emulsions of polydimethylsiloxane/polymers in nonionic surfactants at viscosities of at least about 10,000 cs.
  • substantivity agents form mucoadhesive gels in the presence of saliva, which are substantive to biofilm-coated enamel and gradually dissolve under saliva flow, releasing stannous fluoride onto the biofilm on the enamel at a pH of at least about 3; thereby effecting EPF and ERF values of at least about 2.5 and about 200, respectively.
  • substantivity agents include saliva soluble, aqueous-free emulsions comprised of: polydimethylsiloxane polymers in solid, nonionic surfactants, as described in U.S. Patents: 5,032,387; 5,098,71 1 ; 5,538,667; 5,645,841 ; 5,651 ,959; having the following structural formula:
  • liquid nonionic surfactants comprise the continuous phase of the aqueous-free emulsions.
  • PDMS polydimethylsiloxane
  • Solid surfactants, useful as adjuncts to the liquid nonionic surfactant continuous phase are described in detail in U.S. 5,651 ,959.
  • polydimethylsiloxanes are selected from the group consisting of polydimethylsiloxane: at 1 500 cs, at 1 0,000 cs, at 1 00,000 cs, at 250,000 cs, at 500,000 cs, at 750,000 cs, at 1 .5 million cs, at 2.2 million cs, at 2.5 million cs and combinations thereof.
  • copolymers described below are useful as substantivity enhancers; when combined with the aqueous-free, substantivity agents of the present invention.
  • substantivity enhancers include various linear polymeric, polycarboxylates, such as: copolymers of sodium and calcium salts of methyl/vinyl/ether/maleic acid including those copolymers available commercially as Gantrez® MS-955 polymer, a mixed sodium and calcium salt of methyl/vinyl/ether/maleic acid copolymer; where the cations form salt bridges which cross-link the polymer chains.
  • the chemical structure of this copolymer is represented by the following chemical structure:
  • m is an integer that provides molecular weight for the polymer between about 60,000 and about 500,000.
  • Sodium and calcium salts of carboxymethyl cellulose ether polymers can also be used including sodium and calcium salts of carboxymethyl cellulose ether, hydroxyethyl cellulose ether, sodium cellulose ether, etc.
  • the contribution of Ca ++ from the copolymer substantivity enhancer to ERF values is illustrated in Figures 5 and 6 of the Drawings and Tables 6 and 7.
  • Crodasinic L 1 .42 gm ; Sucralose, 0.1 8 gm; and insoluble saccharin, 0.56 gm were added with continued stirring for 10 minutes.
  • TEGO betaine CKD 1 .42 gm, was added and stirred for 5 minutes.
  • Sipernat 22S 28.3 gm was added with stirring 2 minutes between each addition.
  • Sipernat 22S was all added, stirring continued for 15 minutes after which Vanillamint, 1 .32 gm, and Multisensate flavor, 0.1 14 gm, were added with continued stirring for 5 minutes.
  • the stirrer was removed and the gel was filled into dispensing tubes. When used as a brushing gel, a pleasant, refreshing mouthfeel and very little metallic taste is perceived.
  • Example 2 When used as a brushing gel, a pleasant, refreshing mouthfeel and very little metallic taste is perceived.
  • Example 2 Using the procedure described in Example 1 , a second brushing gel was formulated without the Gantrez MS-955 substantivity enhancer.
  • the test was performed using preheated (37°C) tooth sets and lactate buffer.
  • the deprotected tooth sets were mounted on 1 /4 inch diameter acrylic rods with molten red boxing wax.
  • Multiplaced stirrers were used for treatments and the etches. All slurries and solutions were pre-heated to 37 °C. The actual treatments and etches were carried out on the bench top with the preheated solutions.
  • Plastic specimen containers 120 ml) were used for the etching procedure. A 1 /4 inch hole was drilled in each container lid to accommodate the plastic rod to which the tooth sets were mounted. A 40 ml portion of 0.1 M lactic acid buffer was placed in each container along with a one-inch magnetic stirring bar.
  • the rod of the first tooth set was pushed through the hole in the lid, placed in the first container and adjusted so that all enamel surfaces were immersed into the buffer solution.
  • the container was then placed on the first magnetic stirrer and stirring was begun. The timer was started at this time. At 30-second intervals the other tooth sets were started in the same manner.
  • the first set was stopped and the lid and tooth set immediately removed from the container and placed in a tray of distilled water to terminate etching.
  • the other sets were similarly removed at 30 second intervals in the same order that they were initiated and the lactate buffer solutions was retained for phosphorus analysis.
  • the tooth sets were placed back in the 37 °C water bath in preparation for the fluoride treatment step.
  • the treatments were performed using slurries of the fluoride brushing products.
  • the slurries consisted of 1 part fluoride brushing product and 3 parts preheated (37 Q C) distilled water (9g :27ml). Each slurry was mixed for exactly one minute after adding the water.
  • the slurries were NOT prepared ahead of time. They were NOT centrifuged. All tooth sets were treated at the same time (one for each fluoride brushing product).
  • the treatment procedure was similar to the etching procedure with the exception of the slurry in place of the acid.
  • a 30 ml portion of the preheated fluoride brushing slurry was added to the first tooth set, the teeth were immersed in the slurry and the container placed on the first stirrer.
  • the stirrer and timer were started. At 90-second intervals (to allow time for stirring), the other tooth sets were started in the same manner. At the end of the five minutes of treatment, the first set was stopped, the tooth set removed and rinsed well with distilled water. The other sets were removed at 90-second intervals and rinsed well. The treatment fluoride brushing slurries were discarded.
  • a second acid exposure was then performed by the same method as the pre-treatment etch and the lactate buffer solutions were again retained for phosphorus analysis.
  • the pre and post-treatment solutions were analyzed using a Klett-Summerson Photoelectric Colorimeter.
  • the percent of enamel solubility reduction was computed as the difference between the amount of phosphorus in the pre and post acidic solutions, divided by the amount of phosphorus in the pre solution and multiplied by 100.
  • the deionized water negative control was not effective in reducing enamel solubility.
  • the positive fluoride containing controls and the test gel were significantly more effective than the deionized water negative control.
  • the Clinpro 5000® toothpaste was significantly more effective than the negative control.
  • the Test Gel was significantly more effective than the other two positive controls in reducing enamel solubility.
  • the fluoride uptake was established by analyzing fluoride and calcium levels of enamel pre-treatment and enamel post-treatment to determine the change in enamel fluoride attributed to treatment with fluoride containing brushing products.
  • Each enamel specimen was then etched by immersion into 0.5 ml of 1 M HCI0 4 for 15 seconds. Throughout the etch period, the etch solutions were continuously agitated. A sample of each solution was then buffered with TISAB(fluoride ion probe buffer) to a pH of 5.2 (0.25 ml sample, 0.5 ml TISAB and 0.25 ml 1 N NaOH) and the fluoride content of the solution determined by comparison to a similarly prepared standard curve (1 ml std + 1 ml TISAB). For use in depth of each calculation, the Ca content of the etch solution was determined by taking 50 ⁇ and analyzing for Ca by atomic absorption (0.05 ml qs to 5 ml). These data was the indigenous fluoride level of each specimen prior to treatment.
  • the specimens were once again ground and polished as described above. An incipient lesion was formed in each enamel specimen by immersion into a 0.1 M lactic acid/0.2% Carbopol 907 solution for 24 hours at room temperature. These specimens were then rinsed well with distilled water and stored in a humid environment until used. The treatments were performed using slurries of the various fluoride containing brushing products. The flurries consisted of 1 part fluoride containing brushing product and 3 parts distilled water (9g:27ml). Each slurry was mixed for exactly one minute after adding the water. The slurries were NOT prepared ahead of time. They were NOT centrifuged.
  • the 1 2 specimens of each group were then immersed into 25 ml of their assigned slurry with constant stirring (350 rpm) for 30 minutes. Following treatment, the specimens were rinsed with distilled water. One layer of enamel was then removed from each specimen and analyzed for fluoride and calcium as outlined above (i.e. 1 5 second etch). The pretreatment fluoride (indigenous) level of each specimen was then subtracted from post treatment, fluoride value to determine the change in enamel fluoride due to the last treatment.
  • test fluoride containing brushing products were coded as follows:
  • Toothpaste (stannous
  • a 5 liter Ross/Olsa vacuum mixer with internal homogenizer was heated to 80 degrees C while the vessel was charged with 647.15 gm of PEG 400, 2069.2 gm of anhydrous glycerin and 1 219.5 gm of 1 .64% stannous fluoride/glycerin. Anchor stirring at slow speed was begun and continued for 7 minutes.
  • ULTRAMULSION® [(Plurocare L-1220 (90%)) and 2.5 million cs polydimethylsiloxane (10%), 71 gm, was added with homogenizer speed adjusted to 2500 rpm for 1 5 minutes.
  • the anchor stirrer was increased to medium speed and Gantrez MS-955, 47 gm, was added with stirring and homogenizing for 5 minutes.
  • Crodasinic L 35.5 gm
  • TEGO Betaine CKD 35.5 gm
  • Micronized (20 micron D50) calcium fumarate, anhydrous, 71 gm was added with stirring for 5 minutes.
  • Micronized (20 micron) sodium phosphate monobasic, anhydrous, 1 5.3 gm was added with stirring for 5 minutes.
  • Sident 22S, 707.5 gm was added in increments at 2 minutes between additions until all was added. Stirring was continued for 1 5 minutes.
  • the vessel was cooled to ambient temperature over 15 minutes.
  • the contents were dispensed into tubes for use.
  • the brushing gel was pleasant testing with no stannous fluoride aftertaste.
  • Stannous fluoride stability testing was performed on the product.
  • the stannous fluoride brushing gels of the present invention show substantial improvement in EPF and ERF values compared to commercial toothpastes at various fluoride levels as reported in : Tables 2 through 7, Figs. 1 through 6 of the Drawings and Summary Table 8.
  • the ERF values, reported in Table 3 and Fig. 2 for a Crest® PRO- HEALTH® and Clinpro 5000® toothpastes are 170 and 65 respectively, compared to an ERF for the stannous fluoride brushing gel of the present invention of 300.
  • the ERF values reported in Table 7 and Fig. 6 of the Drawings for Crest® PRO-HEALTH® toothpaste is 210 compared to an ERF for the Stannous Fluoride Brushing Gel of the present invention, 1070.
  • Calcium binding to biofilm shifts from a bidentate chelation to a monodentate chelation in the presence of fluoride, freeing up calcium to bind with fluoride, CaF + pair, thereby doubling the calcium binding capacity.
  • Stable fluoride in the brushing gels of the present invention produces marked reduction in calcium binding affinity and approximately doubles calcium binding capacity. In the absence of fluoride, calcium binding to biofilm is bidentate. Stable fluoride in the brushing gels of the present invention compete with biofilm causing calcium binding to biofilm to become monodentate. This allows the binding of about double the quantity of calcium and of CaF + bound to biofilm. Release of fluoride bound by calcium bridging into biofilm fluid as a result of fluoride clearance into saliva will always be accompanied by a corresponding release of calcium which, in turn, potentiates the cariostatic effect of fluoride as indicated in the in vitro testing described in Tables 2 through 7 and Figs. 1 through 6 of the Drawings.
  • At least some of the stable fluoride present in the brushing gels of the present invention is bound to calcium ions (sourced from various calcium salts in the present invention and/or calcium present in the copolymer substantivity enhancer, such as Gantrez® MS- 955). These calcium ions, in turn, are bound to biofilm associated with enamel.
  • a drop in pH follows exposure of plaque to sucrose which removes some anionic groups by neutralization, thereby liberating calcium and fluoride (as CaF + ) at the very sites where these moieties can do the most good.
  • the effectiveness of the Brushing Gel compositions of the present invention depends on three factors: (1 ) substantivity of the formulation to biofilm,
  • Fluoride binding produces a marked reduction in calcium binding affinity, along with a doubling of calcium binding capacity. This indicates that calcium binding changes from bidentate to monodentate. This shift from bidentate to monodentate is a consequence of fluoride replacing an anionic group as one of the calcium ligends.
  • the anionic groups to which calcium is no longer bound are then free to bind a CaF + ion pair, resulting in a doubling of the calcium binding capacity. Release of fluoride, bound by calcium bridging into plaque fluid, may be accompanied by a release of calcium which will potentiate the cariostatic effect of fluoride.
  • CaF + is taken up by hydroxyapatite and is responsible for the EPF and ERF in vitro data reported for the compositions of the present invention.
  • the ERF values reported in Tables 3 through 8 and Figures 2 through 6 of the Drawings suggest that the CaF + moiety is incorporated into the hydroxyapatite lattice during remineralization.
  • the brushing gels of the present invention set a new, oral care standard for Enamel Protection and Enamel Repair, while dramatically reducing exposure to elevated fluoride levels in various fluoride varnishes, gels and toothpastes.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
  • Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dispersion Chemistry (AREA)
  • Cosmetics (AREA)

Abstract

L'invention concerne des gels pour brossage, sensiblement anhydres, pour la protection et la réparation de l'émail, contenant : du fluorure stanneux, du calcium et un agent de substantivité comprenant : une émulsion de polydiméthylsiloxane dans un tensioactif non-ionique, la substantivité dudit fluorure stanneux et dudit calcium dans le biofilm présent sur l'émail étant renforcée par un déplacement de la liaison du calcium, d'un état bidenté à un état monodenté, en présence de fluorure stanneux ; et lesdits gels pour brossage ayant des valeurs sensiblement améliorées du facteur de protection de l'émail (EPF) et du facteur de réparation de l'émail (ERF) par comparaison avec des traitements par brossage au fluorure ayant des niveaux comparables ou plus élevés de fluorure.
PCT/US2015/025385 2014-04-11 2015-04-10 Gels de brossage pour la protection et la réparation de l'émail WO2015157679A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14/251,149 2014-04-11
US14/251,149 US9586064B2 (en) 2012-10-12 2014-04-11 Enamel protectant and repair brushing gels

Publications (1)

Publication Number Publication Date
WO2015157679A1 true WO2015157679A1 (fr) 2015-10-15

Family

ID=54288449

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2015/025385 WO2015157679A1 (fr) 2014-04-11 2015-04-10 Gels de brossage pour la protection et la réparation de l'émail

Country Status (1)

Country Link
WO (1) WO2015157679A1 (fr)

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6159449A (en) * 1997-04-03 2000-12-12 Enamelon, Inc. Dentifrice products and methods for remineralizing and/or mineralizing teeth
WO2001026577A1 (fr) * 1999-10-08 2001-04-19 Wiesel Peter E Procedes et appareil pour traitement dentaire
US20030165442A1 (en) * 1999-11-12 2003-09-04 The Procter & Gamble Company Method of protecting teeth against erosion
US20030198604A1 (en) * 2000-10-25 2003-10-23 The Procter & Gamble Company Dental care compositions
US20040126335A1 (en) * 1999-11-12 2004-07-01 The Procter & Gamble Company Method of enhancing fluoridation and mineralization of teeth
US20080069781A1 (en) * 2006-09-19 2008-03-20 Ceramoptec Industries Inc. Treatment of periodontal disease with photosensitizers
US20080247973A1 (en) * 1999-11-12 2008-10-09 Arif Ali Baig Compositions and Methods for Improving Overall Tooth Health and Appearance
US20100330003A1 (en) * 2008-02-08 2010-12-30 Colgate-Palmolive Company Oral care product and methods of use and manufacture thereof
WO2013039906A1 (fr) * 2011-09-12 2013-03-21 Mavrik Dental Systems, Ltd. Dispositifs, systèmes et procédés pour le blanchiment des dents
US20130344120A1 (en) * 2012-06-21 2013-12-26 Douglas Craig Scott Mouth Rinse Emulsions
WO2014001132A1 (fr) * 2012-06-25 2014-01-03 Dow Corning France Sas Procédé destiné au traitement thérapeutique d'un substrat kératineux, d'une membrane muqueuse ou d'une dent

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6159449A (en) * 1997-04-03 2000-12-12 Enamelon, Inc. Dentifrice products and methods for remineralizing and/or mineralizing teeth
WO2001026577A1 (fr) * 1999-10-08 2001-04-19 Wiesel Peter E Procedes et appareil pour traitement dentaire
US20030165442A1 (en) * 1999-11-12 2003-09-04 The Procter & Gamble Company Method of protecting teeth against erosion
US20040126335A1 (en) * 1999-11-12 2004-07-01 The Procter & Gamble Company Method of enhancing fluoridation and mineralization of teeth
US20080247973A1 (en) * 1999-11-12 2008-10-09 Arif Ali Baig Compositions and Methods for Improving Overall Tooth Health and Appearance
US20030198604A1 (en) * 2000-10-25 2003-10-23 The Procter & Gamble Company Dental care compositions
US20080069781A1 (en) * 2006-09-19 2008-03-20 Ceramoptec Industries Inc. Treatment of periodontal disease with photosensitizers
US20100330003A1 (en) * 2008-02-08 2010-12-30 Colgate-Palmolive Company Oral care product and methods of use and manufacture thereof
WO2013039906A1 (fr) * 2011-09-12 2013-03-21 Mavrik Dental Systems, Ltd. Dispositifs, systèmes et procédés pour le blanchiment des dents
US20130344120A1 (en) * 2012-06-21 2013-12-26 Douglas Craig Scott Mouth Rinse Emulsions
WO2014001132A1 (fr) * 2012-06-25 2014-01-03 Dow Corning France Sas Procédé destiné au traitement thérapeutique d'un substrat kératineux, d'une membrane muqueuse ou d'une dent

Similar Documents

Publication Publication Date Title
US9604078B2 (en) Methods for protecting and reparing enamel
JP5816549B2 (ja) 生体活性ガラスを用いたフッ化物取り込みを良くするための組成物及び方法
Ali et al. An in-vitro evaluation of fluoride content and enamel remineralization potential of two toothpastes containing different bioactive glasses
Bajaj et al. Comparison of CPP-ACP, tri-calcium phosphate and hydroxyapatite on remineralization of artificial caries like lesions on primary enamel-An in vitro study
JP2016503036A (ja) オーラルケア組成物
CN110087619A (zh) 口腔护理组合物和使用方法
AU2009299913B2 (en) Dentifrice composition comprising fluoride ions and a thickening system
Abdelaziz et al. Effect of two remineralizing agents on microhardness of initial enamel carieslike lesions in young permanent teeth
Schemehorn et al. Comparison of the incipient lesion enamel fluoride uptake from various prescription and OTC fluoride toothpastes and gels
CA2945330C (fr) Procedes pour la protection et la reparation de l'email
WO2015157687A2 (fr) Traitements de type pâte dentifrice de protection et de réparation de l'émail
CA2945337C (fr) Pate dentifrice pour la protection et la reparation de l'email
WO1998042297A1 (fr) Procede de recalcification des dents
WO2015157679A1 (fr) Gels de brossage pour la protection et la réparation de l'émail
JPH06501698A (ja) 口腔衛生調剤
NS et al. Comparative Analysis of Remineralizing Potential of Three Commercially Available Agents-An in Vitro Study

Legal Events

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

Ref document number: 15776669

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15776669

Country of ref document: EP

Kind code of ref document: A1