WO2007141330A1 - nouveaux composés - Google Patents

nouveaux composés Download PDF

Info

Publication number
WO2007141330A1
WO2007141330A1 PCT/EP2007/055654 EP2007055654W WO2007141330A1 WO 2007141330 A1 WO2007141330 A1 WO 2007141330A1 EP 2007055654 W EP2007055654 W EP 2007055654W WO 2007141330 A1 WO2007141330 A1 WO 2007141330A1
Authority
WO
WIPO (PCT)
Prior art keywords
polymer
oral care
acrylate
dentine
integer
Prior art date
Application number
PCT/EP2007/055654
Other languages
English (en)
Inventor
Eugen Barbu
David Raymond Churchley
Thomas Geoffrey Nevell
Gareth David Rees
John Tsibouklis
Original Assignee
Glaxo Group Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Glaxo Group Limited filed Critical Glaxo Group Limited
Publication of WO2007141330A1 publication Critical patent/WO2007141330A1/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
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8141—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 only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • A61K8/8152—Homopolymers or copolymers of esters, e.g. (meth)acrylic acid esters; Compositions of derivatives of such polymers
    • 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
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/10—Esters
    • C08F220/26—Esters containing oxygen in addition to the carboxy oxygen
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/10—Esters
    • C08F220/22—Esters containing halogen
    • C08F220/24—Esters containing halogen containing perhaloalkyl radicals

Definitions

  • the present invention relates to a novel polymer, to a process for its preparation, to oral care compositions comprising such polymer and to its use in the prevention, inhibition and treatment of dental erosion, tooth wear, dentine hypersensitivity, anti-staining of dental enamel and anti-adhesion of oral bacteria.
  • Tooth mineral is composed predominantly of calcium hydroxyapatite, Ca I o(PO 4 MOH) 2 , which may be partially substituted with anions such as carbonate or fluoride, and cations such Zn and Mg. Tooth mineral may also contain non-apatitic mineral phases such as octacalcium phosphate and calcium carbonate.
  • Tooth loss may occur as a result of dental caries, which is a multifactorial disease where bacterial acids such as lactic acid produce sub-surface demineralisation that does not fully remineralise, resulting in progressive tissue loss and eventually cavity formation.
  • bacterial acids such as lactic acid produce sub-surface demineralisation that does not fully remineralise, resulting in progressive tissue loss and eventually cavity formation.
  • acidogenic bacteria such as S. mutans may become pathogenic when levels of easily fermentable carbohydrate, such as sucrose, are elevated for extended periods of time.
  • Dental erosion i.e. acid erosion or acid wear
  • acid erosion is a surface phenomenon that involves demineralisation, and ultimately complete dissolution of the tooth surface by acids that are not of bacterial origin.
  • the acid will be of dietary origin, such as citric acid from fruit or carbonated drinks, phosphoric acid from cola drinks and acetic acid such as from vinaigrette.
  • Dental erosion may also be caused by repeated contact with hydrochloric acid (HCl) produced by the stomach, which may enter the oral cavity through an involuntary response such as gastroesophageal reflux, or through an induced response as may be encountered in sufferers of bulimia.
  • HCl hydrochloric acid
  • Tooth wear is caused by attrition and/or abrasion. Attrition occurs when tooth surfaces rub against each other, a form of two-body wear. An often dramatic example is that observed in subjects with bruxism, a grinding habit where the applied forces are high, and is characterised by accelerated wear, particularly on the occlusal surfaces. Abrasion occurs as a result of three-body wear and the most common example is that associated with brushing with a toothpaste. In the case of fully mineralised enamel, levels of wear caused by commercially available toothpastes are minimal and of little or no clinical consequence. However, if enamel has been demineralised and softened by exposure to an erosive challenge, the enamel becomes more susceptible to tooth wear. Dentine is much softer than enamel and consequently is more susceptible to wear. Subjects with exposed dentine should avoid the use of highly abrasive toothpastes, such as those based on alumina. Again, softening of dentine by an erosive challenge will increase susceptibility of the tissue to wear.
  • Dentine is a vital tissue that in vivo is normally covered by enamel or cementum depending on the location i.e. crown versus root respectively. Dentine has a much higher organic content than enamel and its structure is characterised by the presence of fluid-filled tubules that run from the surface of the dentine-enamel junction to the odontoblast/pulp interface. It is widely accepted that the origins of dentine hypersensitivity relate to changes in fluid flow in exposed tubules, the hydrodynamic theory, that result in stimulation of mechanoreceptors thought to be located close to the odontoblast/pulp interface.
  • an occlusive mixture comprised predominantly of minerals and proteins derived from dentine itself, but also contains organic components from saliva. Over time, the lumen of the tubule may become progressively occluded with mineralised tissue. The formation of reparative dentine in response to trauma or chemical irritation of the pulp is also well documented. Nonetheless, an erosive challenge can remove the smear layer and tubule "plugs" causing outward dentinal fluid flow, making the dentine much more susceptible to external stimuli such as hot, cold and pressure. As previously indicated, an erosive challenge can also make the dentine surface much more susceptible to wear.
  • dentine hypersensitivity worsens as the diameter of the exposed tubules increases, and since the tubule diameter increases as one proceeds in the direction of the odontoblast/pulp interface, progressive dentine wear can result in an increase in hypersensitivity, especially in cases where dentine wear is rapid.
  • WO9616630 claims the use of fluorocarbon-containing coatings to reduce adhesion of bacteria and proteinaceous substances to the surfaces of the oral environment.
  • EP0310919 claims the use of adhesive fluoropolymer compositions for bonding and as a composite resin for hard tissue restorations.
  • the present invention provides a comb fluoropolymer of formula (I):
  • R is H or a C 1 - Ci 0 alkyl group
  • R 1 is H or CH 3
  • R 2 is trifluoromethyl or branched perfluoroalkyl group
  • y is an integer between 1 and 1,000,000,000
  • z is an integer between 0 and 1 ,000,000
  • n is an integer between 1 and 100
  • m in an integer between 1 and 100, with the proviso that y + z > 100.
  • polymers prepared in the bulk, in suspension or in solution have typical number- average molecular weights (GPC, polymethyl methacrylate standards) in the range 0.8 ⁇ 10 4 to 1.2 x 10 5 and polydispersity indexes in the range 1.7 - 12.9.
  • materials prepared in emulsion have preferred number-average molecular weights (GPC, polymethyl methacrylate standards) in the range 0.7 x 10 6 to 1.0 ⁇ 10 6 and polydispersity indexes in the range 1.7 - 2.3.
  • n is from 1 to 20, more suitably 6 to 12.
  • m is from 1 to 10, more suitably 1 to 3.
  • the ratio of y to z ranges from 1 :10 to 10: 1, suitably 1 :5 to 5: 1 and more suitably from 1 :2 to 2: 1.
  • fluoropolymers polymers are: PPFDA - poly(perfluorodecyl acrylate); PPFDMA - poly(perfluorodecyl methacrylate); PNFBEA - poly(nonafluorobutylethyl acrylate), and 2/1 A (2:1 copolymer of IH, IH, 2 1 H 2 'H-perfluorodecyl acrylate and 2- hydroxyethyl acrylate).
  • Fluoropolymers of the present invention may be synthesised by the radical-induced, chain- growth polymerisation reaction of the appropriate monomer or mixture of monomers to yield the corresponding homopolymer or copolymer. Dependant upon the demands of the preferred formulation system and within the reactivity limitations of each monomer type, such reactions may be carried out in the bulk, in solution, in suspension or in an emulsion.
  • the polymers of the present invention are nanoparticles with a size range of from about 1 to 999nm, more suitably 10 to 500nm and most suitably 80 to lOOnm.
  • polymers of the present invention are suitably prepared as aqueous suspensions. More suitably the polymers of the present invention are prepared as an aqueous nano-suspension by emulsion polymerisation.
  • an oral care composition for the reduction or prevention of dental erosion, tooth wear and dentine hypersensitivity comprising a comb fluropolymer of formula (I).
  • compositions of the present invention comprise from 0.01 - 90% w/w of fluoropolymer, more suitably 0.1 to 10% w/w.
  • fluoropolymer is present in the composition as an aqueous nanosuspension with a particle size in the range of 1 to 999nm.
  • compositions of the present invention have also been found to be useful in anti-staining of dental enamel and in anti-adhesion of oral bacteria to dental tissue.
  • compositions of the present invention will further comprise a source of soluble fluoride ions such as those provided by sodium fluoride, sodium monofluorophosphate, tin (II) fluoride or an amine fluoride in an amount to provide from 25 to 3500 ppm fluoride, preferably from 100 to 1500 ppm.
  • a source of soluble fluoride ions such as those provided by sodium fluoride, sodium monofluorophosphate, tin (II) fluoride or an amine fluoride in an amount to provide from 25 to 3500 ppm fluoride, preferably from 100 to 1500 ppm.
  • compositions of the present invention will contain appropriate formulating agents such as abrasives, surfactants, thickening agents, humectants, flavouring agents, sweetening agents, opacifying or colouring agents, preservatives and water, selected from those conventionally used in the oral care composition art for such purposes.
  • appropriate formulating agents such as abrasives, surfactants, thickening agents, humectants, flavouring agents, sweetening agents, opacifying or colouring agents, preservatives and water, selected from those conventionally used in the oral care composition art for such purposes. Examples of such agents are as described in EP 929287.
  • oral care actives may also be included in the compositions of the present invention.
  • the oral compositions of the present invention are typically formulated in the form of toothpastes, sprays, mouthwashes, gels, lozenges, chewing gums, tablets, pastilles, instant powders, oral strips and buccal patches.
  • the efficacy of oral care compositions containing fluoropolymers of the present invention to prevent and/or treat dentine hypersensitivity may be further enhanced by inclusion of a nerve- desensitising potassium salt such as potassium citrate, potassium chloride, potassium bicarbonate, potassium gluconate and especially potassium nitrate.
  • a nerve- desensitising potassium salt such as potassium citrate, potassium chloride, potassium bicarbonate, potassium gluconate and especially potassium nitrate.
  • the compositions of the present invention may also contain additional occlusion agents whose mode of action involves reaction in situ such as strontium salts of chloride, acetate or nitrate.
  • Additional passive occlusion agents that may be incorporated into the compositions of the present invention include silicas, titanium oxide and organic thickening systems such as cellulose polymers, guar gum and polyacrylic acid.
  • compositions according to the present invention may be prepared by admixing the ingredients in the appropriate relative amount in any order that is convenient and thereafter, and if necessary, adjustment of the pH to the desired value.
  • the present invention provides a method of combating dental erosion and/or tooth wear and preventing or treating dentine hypersensitivity which comprises applying an effective amount of a composition comprising a fluoropolymer as herein before described to an individual in need thereof. Additionally, such a composition has benefit in treating caries.
  • IH, 2 H, 2 H-perfluorodecyl acrylate (inhibitor-free; 15.0 g, 28.9 mmol) in perfluorodecalin (2.68 g; 5.80 mmol) was added sodium dodecyl sulphate (SDS) (750 mg) in deionised water (DI) (85 g).
  • SDS sodium dodecyl sulphate
  • DI deionised water
  • the resultant mixture was sonicated (0 0 C, 40 min) to form an emulsion. This was transferred to a 5-necked reaction vessel equipped with an overhead stirrer, double-walled condenser, nitrogen inlet and dropping funnel and was degassed by nitrogen purge (2 h).
  • Mini-emulsions were also prepared with 7H,7H,2H,2H-perfluorodecyl methacrylate, 7H ) 7H,2H,2H-perfluorohexyl acrylate and 7H7H-perfluorobutyl acrylate.
  • Propan-2-ol was added to each tube (1 g of monomer to 2 ml of freshly distilled propan-2-ol) along with 1,1-azobiscyclohexanecarbonitrile (1 %w/w of monomer).
  • the tubes were placed in an oil bath (70 0 C, 72 h) and, following the removal of propan-2-ol by rotary evaporation, the isolated polymeric products were purified by Soxhlet extraction (methanol or diethyl ether) and dried in vacuo (0.5 mbar, 8 h, room temperature).
  • ⁇ ydroxyapatite (HA) -coated microtitre plates were prepared by suspending, with stirring,
  • HA powder (2.0 g) in acetone (200 ml). Aliquots (60 ⁇ l) of the homogenous suspension were transferred into a 96 well polystyrene microtitre plate, and then placed on an orbital shaker operating at 50 rpm (room temperature). After evaporation of the acetone, loosely bonded HA was removed by rinsing the plates with DI (x5). The coated microplates were dried overnight and sealed until required. Prior to use, the HA plates were hydrated in DI for 60 min. Aqueous suspensions of the polymer under test (1.0 % w/v; 200 ⁇ l) were added to each well and the plate transferred to an orbital shaker (50 rpm) at room temperature for 30 min.
  • Sodium fluoride (300 ⁇ g ml "1 fluoride ion) and deionised water were employed as the positive and negative controls respectively.
  • the plates were rinsed (x5) with DI and 0.10 M aqueous acetate buffer (200 ⁇ l, pH 4.0) was added to each well, as an erosive challenge.
  • the microplate was repositioned on the orbital shaker for a further 60 min. Thereafter, aliquots (50 ⁇ l) were removed from each well into a new microplate plate containing vanadomolybdate reagent (50 ⁇ l per well). After a further 5 min, phosphate release was determined by measuring the absorbance at 450nm using a 96 well plate reader (Wallac Victor 1420 Multilabel Counter).
  • PPFDA poly(perfluorodecyl acrylate); PPFDMA - poly(perfluorodecyl methacrylate); PNFBEA - poly(nonafluorobutylethyl acrylate); 2/1 A (2:1 copolymer of lH,lH,2H,2H-perf[uorodecyl acrylate and 2-hydroxy ethyl acrylate).
  • Dentine discs were prepared by sectioning the tooth parallel to the occlusal surface below the crown and above the root canal. Dentine discs were stored in 0.90 % saline until required. To remove the smear layer formed during cutting and expose the dentinal tubules, the dentine discs were etched in aqueous EDTA (0.50 M) for two minutes. Hydraulic conductance (Hc) experiments were performed using a Pashley flow apparatus according to established procedures [1,2].
  • PPFDMA, PNFBEA and 2/1 A were selected for screening in the Hc model.
  • the disodium salt of octadecene-c ⁇ -1-maleic acid (PA- 18) is a tubule occlusion agent that is used commercially in a number of anti-sensitivity toothpastes.
  • Aqueous dispersions (1.0 % w/w) of the polymers were applied to dentine specimens by brushing, and the Pashley flow apparatus was used to determine permeability to simulated dentinal fluid; the permeability of the uncoated, but pellicilised, dentinal specimen provided the baseline value for each measurement.
  • FIG. 2 Reduction in dentine permeability to simulated dentinal fluid following treatment of specimens with selected fluoropolymers and with the PA-18 positive control.
  • the data, summarised in Figure 2 show that all three fluoropolymer coatings effect a reduction in dentinal permeability.
  • the copolymer 2/1 A which reduced dentinal permeability by 54%, exhibited a statistically superior occlusion capacity than that achieved with PDFDMA or with PNFBEA (p ⁇ 0.05); its performance was not statistically different from that of PA- 18, the positive control, which was found to reduce dentinal permeability by 62%.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Cosmetics (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)

Abstract

La présente invention a pour objet un polymère original, un procédé de préparation, des compositions de soins buccaux comprenant un tel polymère et son utilisation pour la prévention, l'inhibition et le traitement de l'érosion dentaire, de l'usure dentaire, de l'hypersensibilité dentinaire, pour le traitement anti-taches de l'émail dentaire et anti-adhésif des bactéries buccales.
PCT/EP2007/055654 2006-06-09 2007-06-08 nouveaux composés WO2007141330A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0611493.8 2006-06-09
GB0611493A GB0611493D0 (en) 2006-06-09 2006-06-09 Novel compounds

Publications (1)

Publication Number Publication Date
WO2007141330A1 true WO2007141330A1 (fr) 2007-12-13

Family

ID=36745651

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2007/055654 WO2007141330A1 (fr) 2006-06-09 2007-06-08 nouveaux composés

Country Status (2)

Country Link
GB (1) GB0611493D0 (fr)
WO (1) WO2007141330A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4292029A (en) * 1978-05-15 1981-09-29 University Of Michigan Hydrophobic composite restorative materials and their use in tooth treatment
EP0182516A1 (fr) * 1984-10-25 1986-05-28 Nitto Denko Corporation Emulsion aqueuse d'un copolymère d'acide acrylique
EP0310919A2 (fr) * 1987-09-28 1989-04-12 Daikin Industries, Limited Composition adhésive pour les biomatériaux

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4292029A (en) * 1978-05-15 1981-09-29 University Of Michigan Hydrophobic composite restorative materials and their use in tooth treatment
EP0182516A1 (fr) * 1984-10-25 1986-05-28 Nitto Denko Corporation Emulsion aqueuse d'un copolymère d'acide acrylique
EP0310919A2 (fr) * 1987-09-28 1989-04-12 Daikin Industries, Limited Composition adhésive pour les biomatériaux

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHIANTORE O ET AL: "Photochemical stability of partially fluorinated acrylic protective coatings I. Poly(2,2,2-trifluoroethyl methacrylate) and poly(1H,1H,2H,2H-perfluorodecyl methacrylate-co-2-ethylhexyl methacrylate)s", POLYMER DEGRADATION AND STABILITY, BARKING, GB, vol. 67, no. 3, 1 March 2000 (2000-03-01), pages 461 - 467, XP004294878, ISSN: 0141-3910 *

Also Published As

Publication number Publication date
GB0611493D0 (en) 2006-07-19

Similar Documents

Publication Publication Date Title
TWI522120B (zh) 包含鋅－胺基酸複合物的口腔用凝膠
TWI513469B (zh) 包括四元氯化鋅與三甲甘胺酸之口腔護理產品
WO2018118138A1 (fr) Compositions de soins buccaux
US20100260849A1 (en) Remineralizing compositions and methods
MX2015007787A (es) Composiciones para el cuidado oral que contienen halogenuros de aminoacido de zinc.
AU2005306867A1 (en) Dental fillers and compositions including phosphate salts
US20210251879A1 (en) Block copolymers for tooth enamel protection
EA027276B1 (ru) Композиция для ухода за полостью рта
Fan et al. Formulation and characterization of antibacterial fluoride-releasing sealants
US10238595B2 (en) Ablative, renewable, multi-functional protective coating for dental surfaces
RU2712141C2 (ru) Композиции для ухода за полостью рта и способы применения композиций
WO2007141330A1 (fr) nouveaux composés
JP2008184436A (ja) 知覚過敏抑制性歯科用研磨材組成物
JP4832129B2 (ja) 歯科用組成物
Özveren et al. Microhardness and SEM-EDX Analysis of Permanent Enamel Surface Adjacent to Fluoride-releasing Restorative Materials Under Severe Cariogenic Challenges.
US11273113B2 (en) Protection of materials by sphingosine based compounds
EP2373280A1 (fr) Nouvel usage
JP7272214B2 (ja) デンタルプラーク・ステイン付着防止剤および口腔用組成物
EP3614994B1 (fr) Composition de protection orale
Upson et al. Polymeric coatings for dental care
Almusa Chemical Analysis of Dental Adhesives and Their Application with Self-Sealing Composites

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: 07730011

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: 07730011

Country of ref document: EP

Kind code of ref document: A1