WO2007065856A1 - Compositions de soin oral comprenant des nanocristaux d'apatite en forme de bâtonnets - Google Patents

Compositions de soin oral comprenant des nanocristaux d'apatite en forme de bâtonnets Download PDF

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Publication number
WO2007065856A1
WO2007065856A1 PCT/EP2006/069194 EP2006069194W WO2007065856A1 WO 2007065856 A1 WO2007065856 A1 WO 2007065856A1 EP 2006069194 W EP2006069194 W EP 2006069194W WO 2007065856 A1 WO2007065856 A1 WO 2007065856A1
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WO
WIPO (PCT)
Prior art keywords
fluoride
rod
composition according
acid
enamel
Prior art date
Application number
PCT/EP2006/069194
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English (en)
Inventor
Christabel Fowler
Charles Richard Parkinson
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 WO2007065856A1 publication Critical patent/WO2007065856A1/fr

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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
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/24—Phosphorous; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • 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
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/41—Particular ingredients further characterized by their size
    • A61K2800/413—Nanosized, i.e. having sizes below 100 nm

Definitions

  • the present invention relates to oral care compositions comprising rod-shaped apatite nanocrystals effective for combating (ie preventing, inhibiting and/or treating) dental erosion and/or tooth wear. Such compositions may also have benefit in combating dental caries and/or dental hypersensitivity.
  • Tooth mineral is composed predominantly of calcium hydroxyapatite, Caio(P0 4 ) 6 (OH) 2 , which may be partially substituted with anions such as carbonate or fluoride, and cations such as zinc or magnesium. 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 Streptococcus 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 maybe 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 typically 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 or dentine-cementum 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.
  • dentine is sensitive since it is generally covered with a smear layer; an occlusive mixture comprised predominantly of mineral and proteins derived from dentine itself, but also containing 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. Loss of the protective enamel layer through erosion and/or acid-mediated wear will expose the underlying dentine, and are therefore primary aetiological factors in the development of dentine hypersensitivity.
  • US Patent 6919070 describes stomatic compositions (including tooth pastes, tooth creams and gels) for curing microdefects of the basic substance of the dental enamel, eg to prevent the spread of caries, comprising particles of hydroxyapatite with an average particle size in length (1), width (d) and thickness (h) of: 1 from 0.2 ⁇ m to 0.01 ⁇ m, d from 0.1 ⁇ m to 0.001 ⁇ m and h from 0.1 ⁇ m to 0.001 ⁇ m.
  • US 2004/0171471 (BASF) describes the preparation of certain rod-shaped apatite nanocrystals with a specific length to width ratio which can be used to remineralise teeth, can form a mineral protective film and can treat tooth defects such as dental caries.
  • the present invention is based on the discovery that rod-shaped apatite nanocrystals (such as those described in the above-noted BASF patent application) protect dental enamel from acid erosion and/or tooth wear.
  • the present invention provides an oral care composition for combating the increasingly prevalent problem of dental erosion and/or tooth wear which composition comprises rod-shaped apatite nanocrystals.
  • compositions of the present invention have the advantage in strengthening teeth, thereby providing protection from and treatment for dental erosion and/or tooth wear.
  • Compositions of the present invention may also be of use in combating dental caries and / or dental hypersensitivity.
  • Figure 1 describes a graph presenting relative enamel hardness values for human enamel subjected to various treatment regimens using a Duramin Microhardness tester.
  • nanoclays refers to crystals whose dimensions are less than 1 ⁇ m.
  • rod-shaped apatite nanocrystals for use in the present invention are as described in US 2004/00171471 and US Patent 6919070, the contents of which are incorporated herein by reference.
  • compositions of the present invention may further comprise a source of soluble fluoride ions.
  • a source of soluble fluoride ions advantageously protects against dental erosion and/or tooth wear.
  • Suitable sources of fluoride ions for use in the compositions of the present invention include an alkali metal fluoride such as sodium fluoride, an alkali metal monofluorophosphate such a sodium monofluorophosphate, stannous fluoride, or an amine fluoride in an amount to provide from 25 to 3500pm of fluoride ions, for example from 100 to 1500ppm.
  • an alkali metal fluoride such as sodium fluoride
  • an alkali metal monofluorophosphate such as sodium monofluorophosphate
  • stannous fluoride or an amine fluoride in an amount to provide from 25 to 3500pm of fluoride ions, for example from 100 to 1500ppm.
  • 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. Examples of such agents are as described in EP 929287.
  • 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 oral compositions of the present invention may further comprises a desensitising amount of a desensitising agent.
  • desensitising agents include a tubule blocking agent or a nerve desensitising agent and mixtures thereof, for example as described in WO 02/15809.
  • Suitable desensitising agents include a strontium salt such as strontium chloride, strontium acetate or strontium nitrate or a potassium salt such as potassium citrate, potassium chloride, potassium bicarbonate, potassium gluconate and especially potassium nitrate.
  • compositions according to the present invention may be prepared by admixing the ingredients in the appropriate relative amounts in any order that is convenient and if necessary adjusting the pH to give a desired value.
  • the present invention also provides a method of combating dental erosion and/or tooth wear which comprises administering an effective amount of an oral composition as hereinbefore defined to a subject in need thereof.
  • a composition may also have benefit in combating dental caries and/or dental hypersensitivity (especially if it further contains a desensitising agent as hereinbefore described).
  • the invention is further illustrated by the following Example.
  • a Duramin Microhardness Tester was used to assess the protective effect of rod-shaped hydroxyapatite against acid erosion of human enamel.
  • a Vickers indentor was employed, and a load of 1.961N applied for 20 seconds.
  • Figure 1 describes the results obtained. All treatments are statistically superior to water at preventing acid induced softening of enamel, at all acid exposure times. Fluoride statistically outperforms nano hydro xyapatite (HA) after short acid exposure times (i.e. 10 mins), whereas the nano HA statistically outperforms fluoride alone after the longest acid exposure time (i.e. 30 mins). The two individual treatments provide comparable protection against acid at 20 mins exposure. The combination of nano HA and fluoride is statistically superior to either fluoride or nano HA alone at preventing acid induced softening of enamel after 30 mins acid exposure.
  • HA nano hydro xyapatite
  • Figure 1 combines the data for six different crowns subjected to each treatment.
  • the error bars represent standard deviations between the crowns.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nanotechnology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Medical Informatics (AREA)
  • Birds (AREA)
  • Molecular Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Cosmetics (AREA)

Abstract

L'invention concerne une composition de soin oral comprenant des nanocristaux d'apatite en forme de bâtonnets, laquelle sert à lutter contre l'érosion dentaire et/ou l'usure des dents.
PCT/EP2006/069194 2005-12-05 2006-12-01 Compositions de soin oral comprenant des nanocristaux d'apatite en forme de bâtonnets WO2007065856A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0524803.4 2005-12-05
GB0524803A GB0524803D0 (en) 2005-12-05 2005-12-05 Novel compositions

Publications (1)

Publication Number Publication Date
WO2007065856A1 true WO2007065856A1 (fr) 2007-06-14

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GB (1) GB0524803D0 (fr)
WO (1) WO2007065856A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2467739C1 (ru) * 2011-10-31 2012-11-27 Федеральное государственное автономное образовательное учреждение высшего профессионального образования "Белгородский государственный национальный исследовательский университет" Состав стоматологический для лечения гиперестезии зубов
CN103039689A (zh) * 2012-12-10 2013-04-17 宏英工业有限公司 口香糖的制法及其成品
CN104254336A (zh) * 2012-02-10 2014-12-31 派瑞达克有限公司 多成分的口腔保健组合物

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0786245A1 (fr) * 1996-01-24 1997-07-30 Sangi Co., Ltd. Compositions dentaires contenant de l'hydroxyapatite submicrométrique
WO2001001930A2 (fr) * 1999-07-02 2001-01-11 Henkel Kommanditgesellschaft Auf Aktien Materiaux composites constitues de composes de calcium et de composantes proteiques
WO2004028271A1 (fr) * 2002-09-23 2004-04-08 Sus Tech Gmbh & Co. Kg Gomme a macher contenant un sel de calcium
US20040171471A1 (en) * 2001-06-22 2004-09-02 Noerenberg Ralf Rod shaped apatite crystals with a specific length-to-width ratio
WO2005020878A2 (fr) * 2003-09-01 2005-03-10 Henkel Kommanditgesellschaft Auf Aktien Solution dentaire et buccale
WO2006133747A1 (fr) * 2005-06-15 2006-12-21 Henkel Kommanditgesellschaft Auf Aktien Agents a effet remineralisant destines au nettoyage et a l'hygiene des dents et de la bouche

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0786245A1 (fr) * 1996-01-24 1997-07-30 Sangi Co., Ltd. Compositions dentaires contenant de l'hydroxyapatite submicrométrique
WO2001001930A2 (fr) * 1999-07-02 2001-01-11 Henkel Kommanditgesellschaft Auf Aktien Materiaux composites constitues de composes de calcium et de composantes proteiques
US20040171471A1 (en) * 2001-06-22 2004-09-02 Noerenberg Ralf Rod shaped apatite crystals with a specific length-to-width ratio
WO2004028271A1 (fr) * 2002-09-23 2004-04-08 Sus Tech Gmbh & Co. Kg Gomme a macher contenant un sel de calcium
WO2005020878A2 (fr) * 2003-09-01 2005-03-10 Henkel Kommanditgesellschaft Auf Aktien Solution dentaire et buccale
WO2006133747A1 (fr) * 2005-06-15 2006-12-21 Henkel Kommanditgesellschaft Auf Aktien Agents a effet remineralisant destines au nettoyage et a l'hygiene des dents et de la bouche

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2467739C1 (ru) * 2011-10-31 2012-11-27 Федеральное государственное автономное образовательное учреждение высшего профессионального образования "Белгородский государственный национальный исследовательский университет" Состав стоматологический для лечения гиперестезии зубов
CN104254336A (zh) * 2012-02-10 2014-12-31 派瑞达克有限公司 多成分的口腔保健组合物
US9211240B2 (en) 2012-02-10 2015-12-15 Periproducts Ltd Multicomponent oral care composition
US9408788B2 (en) 2012-02-10 2016-08-09 Periproducts Ltd Multicomponent oral care composition
EP3207934A1 (fr) * 2012-02-10 2017-08-23 Periproducts Ltd Composition de protection orale à composants multiples
CN103039689A (zh) * 2012-12-10 2013-04-17 宏英工业有限公司 口香糖的制法及其成品

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Publication number Publication date
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