WO2021078685A1

WO2021078685A1 - Method of reducing dental hypersensitivity

Info

Publication number: WO2021078685A1
Application number: PCT/EP2020/079371
Authority: WO
Inventors: Vaishali Gode; Sembian CHANDRASEKARAN; Neha TRIVEDI
Original assignee: Unilever Ip Holdings B.V.; Unilever Global Ip Limited; Conopco, Inc., D/B/A Unilever
Priority date: 2019-10-23
Filing date: 2020-10-19
Publication date: 2021-04-29

Abstract

Disclosed is non-therapeutic use of a bipolar composite material comprising: (i) a clay whose precursor is an asymmetric 1:1 or 2:1:1 clay particle comprising alternating tetrahedral and octahedral sheets terminating with a tetrahedral sheet at one external surface plane and an octahedral sheet at another; and, (ii) antimicrobial quaternary ammonium compound attached to a coordinating cation on one of said external surface planes, in an oral care composition to reduce dental hypersensitivity.

Description

METHOD OF REDUCING DENTAL HYPERSENSITIVITY

Field of the Invention

The present invention relates to compositions for treating dental hypersensitivity.

Background of the Invention

Dental plaque is a major cause of oral diseases. Plaque acids attack the tooth enamel leading to caries and toxins produced by the plaque cause inflammation of the gums (gingivitis) and eventually gum recession and tooth loss (periodontitis). Recession of the gum from teeth exposes the dentin of the root which can be damaged making the teeth hypersensitive to tactile and/or thermal stimuli. The resultant pain can make toothbrushing uncomfortable thus leading to inefficient plaque removal and further exacerbation of the problem. Hypersensitive teeth are sensitive to at least one of hot food, cold food, sugary food or air.

When the root surfaces are exposed, dentinal tubules are also exposed. Dentinal tubules are naturally present in the dentinal layer of the tooth and they provide for an osmotic flow between the inner pulp region of the tooth and the outer root surfaces. The dentin of the tooth generally contains channels, called tubules, which provide for an osmotic flow between the inner pulp region of the tooth and the outer root surfaces.

The current theory for dental hypersensitivity is called the hydrodynamic theory. It is based on the belief that open exposed dentinal tubules allow fluid flow through the tubules. This flow excites the nerve endings in the dental pulp. Clinical replica of sensitive teeth viewed in a SEM (scanning electron microscopy) reveal varying numbers of open or partially occluded dentinal tubules.

There are different approaches to treat hypersensitivity. One approach is to reduce the excitability of the nerve in sensitive teeth by using "nerve-depolarising agents" comprising strontium ions, potassium salts such as potassium nitrate, potassium bicarbonate or potassium chloride. These nerve-depolarising agents interfere with neural transduction of the pain stimulus to make the nerves less sensitive.

Another approach relies on occluding agents which function by physically blocking the exposed ends of dentinal tubules, thereby reducing dentinal fluid movement and reducing the irritation associated with the shear stress described by the hydrodynamic theory. These tubule blocking agents function by physically blocking the exposed ends of the dentinal tubules, thereby reducing dentinal fluid movement and reducing the irritation associated with the shear stress described by the hydrodynamic theory. An ideal tubule blocking agent should provide faster and longer-lasting tubule occlusion. Tubule occlusion can be achieved either by deposition of mineral crystals on dentine surfaces and/or within the dentinal tubules. Superficial deposition of mineral crystals on dentine surfaces can provide short-term relief but the precipitate can be removed either by daily brushing and/or dissolved by saliva and/or consumption of acidic beverages. Occlusion within the dentinal tubules provides effective treatment with long-term benefit.

An example of an occluding agent is found in US5270031 B1 (Bock Drug Company) which describes a tubule occluding desensitizer comprising a polyacrylic acid such as Carbopol® polymeric materials. Another tubule occluding composition is disclosed in US5374417 B1 (Colgate) which discloses a potassium salt of a synthetic anionic polymer, such as a polycarboxylate.

W01 7182240 A1 (Unilever) discloses an oral care composition comprising a sensitivity mitigating agent, a polymeric deposition aid, the composition having a viscosity 3 weeks from manufacture or longer of from 10,000 to 60,000 cps at 25 degrees centigrade.

W09632090 A1 (Block Drug Co) discloses that hypersensitive teeth can be treated with an oral composition comprising hectorite clay, especially Laponite clay.

US4992258 A (Colgate) discloses dentifrice containing montmorillonite clay for treatment of hypersensitive dentine. WO2019034387 A1 (Unilever) discloses a bipolar composite material comprising: (i) a clay whose precursor is an asymmetric 1:1 or 2:1:1 clay particle, comprising alternating tetrahedral and octahedral sheets terminating with a tetrahedral sheet at one external surface plane and an octahedral sheet at another; and, (ii) antimicrobial quaternary ammonium compound attached to a coordinating cation on one of said external surface planes, in an oral care composition, further comprising at least one source of fluoride ions, for use in promoting remineralization of teeth.

WO2019034352 A1 (Unilever) the same material as aforementioned for use to control staining of teeth due to ammonium compound

Summary of the Invention

It is surprisingly found by the present inventors that a bipolar composite material as disclosed hereinafter reduces dental hypersensitivity.

According to a first aspect disclosed is non-therapeutic use of a bipolar composite material comprising:

(i) a clay whose precursor is an asymmetric 1:1 or 2: 1 : 1 clay particle comprising alternating tetrahedral and octahedral sheets terminating with a tetrahedral sheet at one external surface plane and an octahedral sheet at another; and,

(ii) antimicrobial quaternary ammonium compound attached to a coordinating cation on one of said external surface planes, in an oral care composition to reduce dental hypersensitivity. According to a second aspect disclosed is a non-therapeutic method of reducing dental hypersensitivity comprising a step of applying to teeth an oral care composition comprising a bipolar composite material, wherein said material comprises:

(ii) antimicrobial ammonium compound attached to a coordinating cation on one of said external surface planes.

According to a third aspect disclosed is a bipolar composite material for use in an oral care composition in the treatment of dental hypersensitivity, comprising:

(ii) antimicrobial ammonium compound attached to a coordinating cation on one of said external surface planes. According to a fourth aspect disclosed is use of a bipolar composite material comprising:

(ii) antimicrobial ammonium compound attached to a coordinating cation on one of said external surface planes, in the manufacture of an oral care composition for reducing dental hypersensitivity. These and other aspects, features and advantages will become apparent to those of ordinary skill in the art from a reading of the following detailed description and the appended claims. For the avoidance of doubt, any feature of one aspect of the present invention may be utilised in any other aspect of the invention. The word "comprising" is intended to mean "including" but not necessarily "consisting of" or "composed of." In other words, the listed steps or options need not be exhaustive. It is noted that the examples given in the description below are intended to clarify the invention and are not intended to limit the invention to those examples per se. Except in the operating and comparative examples, or where otherwise explicitly indicated, all numbers in this description and claims indicating amounts of material or conditions of reaction, physical properties of materials and/or use are to be understood as modified by the word "about". Numerical ranges expressed in the format "from x to y" are understood to include x and y. All references to the term/expression wt% or % by weight, shall mean percentage by weight of the composition, except where indicated otherwise. Detailed Description of the Invention

Oral care composition

For the purposes of the present invention, oral care composition means a toothpaste, toothpowder, liquid, gel, serum, orally dissolvable films, tablets, gum or any other preparation for cleaning the teeth or other surfaces in the oral cavity.

Toothpaste

"Toothpaste" for the purpose of the present invention means a paste or gel dentifrice for use with a toothbrush. The paste may be single phase or could have more than one phases such as striped compositions. Particle Size

"Particle size" for the purpose of the present invention means D50 particle size. The D50 particle size of a particulate material is the particle size diameter at which 50 wt% of the particles are larger in diameter and 50 wt% are smaller in diameter. For the purpose of the present invention, particle sizes and distribution are measured using Malvern Mastersizer® 2000 and Malvern ZetaSizer® Nano series.

The pH pH is quoted at atmospheric pressure and a temperature of 25°C. When referring to the pH of an oral care composition, this means the pH measured when 5 parts by weight of the composition is uniformly dispersed and/or dissolved in 20 parts by weight pure water at 25°C. In particular, the pH may be measured by manually mixing 5 g oral care composition with 20 ml_ water for 30 seconds, then immediately testing the pH with an indicator or a pH meter.

The bipolar composite particle

It is preferred that median particle size (D50) of this material is 0.1 to 10 pm, more preferably 0.4 to 1 pm and most preferably 0.5 to 0.8 pm. Lower particle size also provides an effective mechanism for increasing the loading of the antimicrobial quaternary ammonium compound, if so desired.

It is preferred that in the bipolar composite material comprising a clay, the precursor of the clay is an asymmetric 1:1 clay particle. Preferred 1:1 clays include kaolinite and serpentine subgroups of minerals. The species included within the kaolinite subgroup include but are not limited to kaolinite, dickite, halloysite and nacrite. The species within the serpentine subgroup include but are not limited to chrysolite, lizardite, and amesite. Alternatively, it is also preferred that the precursor of the clay is an asymmetric 2:1:1 clay particle. Preferred 2:1:1 clays include chlorite group of minerals. The chlorite comprises tetrahedral-octahedral-tetrahedral sheets like 2:1 clays, with an extra weakly bound brucite like layer between tetrahedral layers. The tetrahedral sheet preferably comprises coordinating tetrahedral cations of silicon. The tetrahedral sheet may also include isomorphously substituted coordinating tetrahedral cations which are not silicon. Isomorphously substituted coordinating tetrahedral cations include, but are not limited to, cations of aluminum, iron or boron. It is preferred that the octahedral sheet has coordinating octahedral cations of aluminum. The octahedral sheet may also comprise isomorphously substituted coordinating octahedral cations which are not aluminium. Isomorphously substituted coordinating octahedral cations include cations of magnesium and iron. The antimicrobial agent is attached to the coordinating cations on the exterior side of one of the external surface planes. Accordingly, the antimicrobial quaternary ammonium compound is attached to coordinating cations on the exterior side of the tetrahedral sheet. Alternatively, the antimicrobial quaternary ammonium compound is attached to the coordinating cations on the exterior side of the octahedral sheet. Coordinating cations on the exterior side of each of the tetrahedral and the octahedral surface sheets are attached to the antimicrobial quaternary ammonium compound, with the proviso that the antimicrobial quaternary ammonium compound attached to the coordinating cations on the exterior side of the tetrahedral surface sheet is not identical to the molecule attached to the coordinating cations on the exterior side of the octahedral surface sheet. The antimicrobial quaternary ammonium compound is preferably attached to the coordinating cations on the external surface of the octahedral surface plane and is not preferably attached to coordination cations of non exterior tetrahedral or octahedral plane or on the interior side of the surface sheets.

It is preferred that the ratio of the clay: antimicrobial quaternary ammonium compound is from 1 :0.001 to 1:1, more preferably from 1 :0.001 and 1:0.1 parts by weight of the bipolar composite material.

It is preferred that in the antimicrobial quaternary ammonium compound, the antibacterial agent is attached to coordinating cations on the external surface of the octahedral surface plane.

Preferably the oral care composition of the invention comprises 0.1 to 10 wt% of the bipolar antimicrobial material, more preferably 0.5 to 5 wt% material. Preferably the quaternary ammonium compound is one or more of cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC), benzethonium chloride, cetrimide, quaternium, tetrabutyl ammonium bromide, undecylenamido propyltrimonium methosulphate, methylbenzethonium chloride, cetethyldimonium bromide, cetromonium tosylate, cocotrimonium chloride, dodecylbenzyltrimonium chloride, lauryl isoquinolium bromide, laurylpyridinium chloride, dequalinium chloride or domiphen bromide.

It is particularly preferred that the antimicrobial agent cetylpyridinium chloride (CPC). Without being bound by theory, it is believed that the primary activity is linked to the cationic charge of its amine group. Thus, cetylpyridinium chloride is attracted to and binds to negatively-charged protein moieties on the cell membrane or cell wall of the microorganism and to tooth surfaces which are also typically negatively charged. The resulting attachment to microorganisms disrupts the cell wall structure causing leakage of the intracellular fluids, eventually killing the associated microorganism. However, as disclosed earlier.

It is particularly preferred that precursor of the clay is a 1:1 clay particle. Further preferably the precursor of the clay is kaolinite. It is particularly preferred that the antimicrobial quaternary ammonium compound is cetyl pyridinium chloride. It is further particularly preferred that when the precursor of the clay is kaolinite, the antimicrobial quaternary ammonium compound is cetyl pyridinium chloride.

The use in accordance with the invention is for non-therapeutic purpose. More particularly it is for cosmetic purpose.

Hypersensitivity

Preferably the dental hypersensitivity is reduced by occlusion or blocking of dentinal tubules. It is further preferred that the use in accordance with the invention brings about at least 70% occlusion or blocking of dentinal tubules as determined by dentine disc tubule occlusion method. Alternatively, and further preferably it is preferred that the dental hypersensitivity is reduced by lowering the hydraulic conductance through dentine. It is further preferred that the hydraulic conduction is reduced by lowering the flow rate of fluid through the dentine.

The description of preferred features applies mutatis mutandis to the other aspects of the invention. For example, description of the preferred features for the use in accordance with this invention also applies mutatis mutandis to the method in accordance with this invention. Carrier

The composition is an oral care composition and typically comprises a physiologically acceptable carrier. The carrier preferably comprises at least surfactant, thickener, humectant or a combination thereof.

Preferably the oral care composition comprises a surfactant. Preferably the composition comprises at least 0.01 wt% surfactant, more preferably at least 0.1 wt% and most preferably from 0.5 to 7 wt%. Suitable surfactants include anionic surfactants, such as the sodium, magnesium, ammonium or ethanolamine salts of C8 to C18 alkyl sulphates (for example sodium lauryl sulphate), C8 to C16 alkyl sulphosuccinates (for example dioctyl sodium sulphosuccinate), C8 to C12 alkyl sulphoacetates (such as sodium lauryl sulphoacetate), C8 to C24 alkyl sarcosinates (such as sodium lauryl sarcosinate), C8 to C24 alkyl phosphates (which can optionally comprise up to 10 ethylene oxide and/or propylene oxide units) and sulphated monoglycerides. Other suitable surfactants include nonionic surfactants, such as optionally polyethoxylated fatty acid sorbitan esters, ethoxylated fatty acids, esters of polyethylene glycol, ethoxylates of fatty acid monoglycerides and diglycerides, and ethylene oxide/propylene oxide block polymers. Other suitable surfactants include amphoteric surfactants, such as betaines or sulphobetaines. Mixtures of any of the above described materials may also be used. More preferably the surfactant comprises or is anionic surfactant. The preferred anionic surfactants are sodium lauryl sulphate and/or sodium dodecylbenzene sulfonate. Most preferably the surfactant is sodium lauryl sulphate, sodium coco sulfate, cocamidopropyl betaine or mixtures thereof. Thickener may also be used in this invention and is limited only to the extent that the same may be added to a composition suitable for use in the mouth. Illustrative examples of the types of thickeners that may be used in this invention include, sodium carboxymethyl cellulose (SCMC), hydroxyl ethyl cellulose, methyl cellulose, ethyl cellulose, gum tragacanth, gum arabic, gum karaya, sodium alginate, carrageenan, guar, xanthan gum, Irish moss, starch, modified starch, silica based thickeners including silica aerogels, magnesium aluminum silicate (e.g., Veegum®), Carbomers (cross-linked acrylates) and mixtures thereof. Typically, xanthan gum and/or sodium carboxymethyl cellulose and/or a Carbomer is/are preferred. When a Carbomer is employed, those having a weight-average molecular weight of at least 700,000 Da are desired, and preferably, those having a molecular weight of at least 1,200,000 Da and most preferably, those having a molecular weight of at least about 2,500,000 Da are desired. Mixtures of Carbomers may also be used herein.

In an especially preferred embodiment, the Carbomer is Synthalen® PNC, Synthalen® KP or a mixture thereof. It has been described as a high molecular weight and cross- linked polyacrylic acid and identified via CAS number 9063-87-0. These types of materials are available commercially from suppliers like Sigma.

In another especially preferred embodiment, the sodium carboxymethyl cellulose (SCMC) used is SCMC 9H. It has been described as a sodium salt of a cellulose derivative with carboxymethyl groups bound to hydroxy groups of glucopyranose backbone monomers and identified via CAS number 9004-32-4. The same is available from suppliers like Alfa Chem. In another especially preferred embodiment, the thickener is xanthan gum. Thickener typically makes up from 0.01 to 10 wt%, more preferably 0.1 to 9 wt%, and most preferably, from 0.1 to 5 wt%.

When the oral care composition of this invention is a toothpaste or gel, the same typically has a viscosity from about 30,000 to 180,000 centipoise, and preferably, from 60,000 to 170,000 centipoise, and most preferably, from 65,000 to 165,000 centipoise. Suitable humectants are preferably used in the oral care composition of the present invention and they include, for example, glycerin, sorbitol, propylene glycol, dipropylene glycol, diglycerol, triacetin, mineral oil, polyethylene glycol (preferably, PEG-400), alkane diols like butane diol and hexanediol, ethanol, pentylene glycol, or a mixture thereof. Glycerin, polyethylene glycol, sorbitol or mixtures thereof are the preferred humectants. The humectant may be present in the range of from 10 to 90 wt%. More preferably, the carrier humectant makes up from 25 to 80 wt%, and most preferably, from 30 to 60 wt%.

Optional & preferred ingredients

The oral care composition may further comprise benefit agents that are typically delivered to teeth or the oral cavity including the gums to enhance or improve a characteristic of those dental tissues. The only limitation with respect to the benefit agents that may be used in this invention is that the same is suitable for use in the mouth.

Preferably the benefit agents include coloring agents, biomineralization agents, antibacterial agents or mixtures thereof. For example, coloring agent such as particulate whitening agents and pigments, preferably a particulate whitening agent. Preferably, the pigment, when used, is violet or blue having a hue angle, h, in the CIELAB system of from 220 to 320 degrees. These pigments may be selected from one or more of those listed in the Colour Index International, listed as pigment blue 1 through to pigment blue 83, and pigment violet 1 through to pigment violet 56.

Biomineralization agents for tooth enamel remineralization may be one or more of amorphous calcium phosphate, otricalcium phosphate, beta -tricalcium phosphate; calcium carbonate, calcium deficient hydroxyapatite (Ca9(HP04)(P04)50H), dicalcium phosphate (CaHP04), dicalcium phosphate dehydrate (CaHP04-2H2O), hydroxyapatite (CaO(P04)6(OH)2), monocalcium phosphate monohydrate (Ca(H2P04)2 H2O), octacalcium phosphate (CasH2(P04)6-5H2O) and tetracalcium phosphate (Ca4(P04)20); antibacterial agents may be selected from one or more of metal salts where the metal is selected from zinc, copper, silver or a mixture thereof, triclosan, triclosan monophosphate, triclocarban, curcumin, quaternary ammonium compounds, bisbiguanides and long chain tertiary amines, preferably zinc salts including zinc oxide, zinc chloride, zinc acetate, zinc ascorbate, zinc sulphate, zinc nitrate, zinc citrate, zinc lactate, zinc peroxide, zinc fluoride, zinc ammonium sulfate, zinc bromide, zinc iodide, zinc gluconate, zinc tartarate, zinc succinate, zinc formate, zinc phenol sulfonate, zinc salicylate, zinc glycerophosphate or a mixture thereof. The benefit agent is preferably particulate as this allows for maximum surface area for contact with dental tissue.

Particulate whitening agent comprise a material suitable to physically and immediately improve characteristics of teeth and especially whiten teeth. In order to provide excellent whitening effect, the material is preferred to have a high refractive index of at least 1.9, more preferably at least 2.0, even more preferably at least 2.2, even more preferably still at least 2.4 and most preferably at least 2.5. The maximum refractive index of the material is not particularly limited but preferably up to 4.0. Preferably, the material has a refractive index ranging from 1.9 to 4.0. Particularly suitable materials are metal compounds and preferred are compounds where the metal is selected from zinc (Zn), titanium (Ti), zirconium (Zr) or a combination thereof. Preferably, the metal compound is (or at least comprises) a metal oxide such as titanium dioxide (Ti02), zinc oxide (ZnO), zirconium dioxide (Zr02) or a combination thereof. In addition, the particulate whitening agent can also comprise non-metal oxides such as silicon monoxide (SiO).

Potassium ions may inhibit the rapid calcium phosphate formation on dentine surfaces, which allows calcium ions and phosphate ions to penetrate deeply into dentinal tubules, nucleate and deposit inside the tubules. The oral care composition of the present invention may comprise a phosphate source. Such phosphate source includes, for example, trisodium phosphate, monosodium dihydrogen phosphate, disodium hydrogen phosphate, sodium pyrophosphate, tetrasodium pyrophosphate, sodium hexametaphosphate, mixtures thereof or the like. The oral care composition of the present invention may contain a variety of other ingredients which are common in the art to enhance physical properties and performance. These ingredients include antimicrobial agents, anti-inflammatory agents, anti-caries agents, plaque buffers, fluoride sources, vitamins, plant extracts, desensitizing agents, anti-calculus agents, biomolecules, flavors, proteinaceous materials, preservatives, opacifying agents, coloring agents, pH-adjusting agents, sweetening agents, particulate abrasive materials, polymeric compounds, buffers and salts to buffer the pH and ionic strength of the compositions, and mixtures thereof. Such ingredients typically and collectively make-up less than 20 wt% by weight of the composition, and preferably, from 0.0 to 15 wt%, and most preferably, from 0.01 to 12 wt%.

The oral care composition is usually packaged in, e.g., a collapsible tube. In tooth paste or gel form, the composition may be packaged in a conventional plastic laminate, metal tube or a single compartment dispenser. The same may be applied to dental surfaces by any physical means, such as a toothbrush, fingertip or by an applicator directly to the sensitive area. The composition can be effective even when used in an individual's daily oral hygiene routine. For example, the composition may be brushed onto the teeth. The composition may, for example, be contacted with the teeth for a time period of one second to 20 hours, such a leave-on overnight gel or serum. More preferably from 1 second to 10 hours, more preferably still from 10 seconds to 1 hour and most preferably from 30 seconds to 5 minutes. The composition may be used daily, for example for use by an individual once, twice or three times per day. When the oral care composition is a dual phase composition, the two phases of the composition are mixed during application. The mixed phases are typically left on the teeth for from 3 minutes to 10 hours, more preferably from 3 minutes to 8 hours. The application may be carried out one to five times monthly. The following examples are provided to facilitate an understanding of the present invention. The examples are not provided to limit the scope of the claims.

Various examples illustrative of the invention are presented as follows and are no way to be considered as limiting the scope of the invention.

Examples

Example 1: Hydraulic conductance through human dentine discs Toothpastes A and B, having the compositions as per Table 1 were prepared.

Table 1

Note*:

*The bipolar composite material contained kaolinite and cetyl pyridinuim chloride in an amount which made the final amount of CPC was 0.045 wt% by total weight of the toothpaste composition. D50 of the composite material was 0.5 pm. The material was made in accordance with Example 1 of US2012/0177712 A1 (Unilever). The protocol for measurement of the hydraulic conductance through human dentine discs after treatment with toothpaste formulations in a 5-day model and to identify any occluding particles using Raman spectroscopy was as follows. This 5-day model procedure measures the change in hydraulic conductance of human dentine discs after treatment with toothpastes.

Treated dentine was analysed using Renishaw confocal microscopy using Raman technique to identify occluding particles within the tubules to measure any change in hydraulic conductance over the test period and to rank the compositions based on their propensity to reduce hydraulic conductance. The one which brought about maximum reduction was judged as the best composition of the set.

There were two variables; the method of application and the duration. For this experiment, an artificial human saliva was prepared. Its composition was as follows:

Table 2

The pH of artificial human saliva was adjusted to 7.0 using NaOH.

Sound, caries-free human molars were sectioned using a wafering saw and dentine discs, approximately 800 mhi thick, were taken from between the crown and the pulp cavity. The discs were polished flat with P800 grit paper to thickness of about 200 mhi. They were then serially polished with a final polish of P2500 grit paper to give a flat polished dentine surface on either side of the disc. The discs were then placed into 1% w/w citric acid solution and sonicated for two minutes and examined under light microscopy to ensure an abundance of open tubules. A disc was placed into a split cell holding chamber which was connected to a pressurized container that delivered artificial human saliva at 1 atm pressure through the dentine disc. The fluid flow rate through the dentine discs was recorded using a Sensirion® liquid flow meter for five minutes. Discs where the flow rate was outside the acceptance criteria of 2 - 10 ul/min or which did not have a steady flow rate after five minutes were discarded. A total of N =10 dentine discs were selected for each treatment group (150 dentine discs in total). The average steady state flow rate over the 5-minute period was then considered as the hydraulic conductance flow rate. The toothpastes were tested using the following methods of application where the duration was 5 seconds and 20 seconds.

1. Finger application of neat paste formulation

2. Application of neat formulation with an electric toothbrush

The procedure was as follows: a) A fresh dentine disc encapsulated within the split cell was attached to the hydraulic conductance apparatus and an initial baseline fluid flow rate was measured, n=10 for each product tested and for each test method. b) The flow of artificial saliva was switched off and the dentine disc blotted briefly to remove excess liquid. c) The dentine was treated using finger application or using an electric toothbrush. d) After treatment, the resulting slurry was left to incubate on the dentine disc for two minutes. e) The dentine disc was then briefly rinsed with deionised water and the flow of artificial saliva switched back on. The treated dentine discs fluid flow rate was then measured. f) After the measurement, the split cell was disconnected from the hydraulic conductance instrument and placed into a container with 50 ml of artificial saliva and incubated at 37°C for six hours. g) The discs were then removed from the artificial saliva and treated again, placed back into the artificial saliva and incubated overnight. h) On the second day, the dentine discs were removed from the artificial saliva, rinsed and the fluid flow rate measured. The discs were then treated and placed back into the artificial saliva for six hours. They were then treated again as described earlier. i) The day-2 procedure was then repeated on three days i.e. the treatment was for a total of five days with two treatments and one fluid flow measurement a day.

Laser confocal microscopy with Raman analysis

After the fifth day, the treated dentine discs were analysed using a Renishaw confocal Raman microscope. Images of the dentine were captured using the confocal microscope and the occluding material identified using Raman analysis. The Raman signals from the treated dentine were calibrated using pure kaolin.

The hydraulic conductance equipment was connected to a compressed air supply and the solvent chamber pressurised to 1.0 psi. A dentin disc was placed into the holding chamber and EBSS Earles balanced salt solution (Sigma-Aldrich) passed through the system. An air bubble was introduced into the capillary tube via the input port and allowed to proceed along the capillary tube for a few seconds before being timed from a defined start point. A record was then made of the start position of the bubble and its progression timed over five minutes and the distance travelled measured at every 1- minute interval.

The test formulation was applied to the dentin disc using a Benda brush for 10 seconds and then left to soak in the formulation for two minutes. The disk was then rinsed with deionised water obtained by reverse osmosis. A second air bubble was introduced into the capillary tube and, after a brief pause, the distance travelled again measured over five minutes with the distance travel recorded at every 1 -minute interval.

The flow rate was calculated by measuring the displacement of liquid from the capillary tube over 5 minutes. The linearity of the flow rate was determined by calculating the r² of distance over time. Every value of occlusion was the result of ten separate determinations. The extent of reduction in fluid flow brought about by each formulation is shown in Table 3 below. Table 3

The data in Table 3 clearly indicates that the compositions A and B bring about a significant reduction in fluid which is a measure of their efficacy. The extent of reduction brought about by compositions A and B were far better than the marketed product.

Example 2: Tubule occlusion of human dentine discs This protocol describes the procedure and method for measuring tubule occlusion using SEM imaging when human dentine discs are treated with toothpaste formulations in a 5-day model. The extent of occlusion of tubules is determined by a Categorical Grading scale of SEM images of the treated dentine. Treated dentine is then analysed using Renishaw confocal microscopy with Raman to identify occluding particles within the tubules.

Sound, caries-free human molars were sectioned, and the discs were examined under light microscopy as described earlier. SEM imaging method

Images of specimen of the dentine were captured without sputter-coating the samples. Each dentine specimen was examined at four different locations at 1500X magnification using secondary electron imaging. A representative image (Se1) of each dentine disc was captured. A topographical image of the same location was also captured. The topographical image was generated by changing the position of the electron gun but keeping the focus of the electrons on the same location. This resulted in highlighting the topographical details of the dentine surface. The Se1 SEM images of the four locations that were visited were used to assess the occlusion using a Categorical Grading scale. The compositions were tested using the two methods as described earlier. Eight human dentine blocks (for each treatment) set in resin discs was examined by SEM and the day-2 procedure was repeated for a further three days at N=8, as earlier.

The results (extent of tubule blocking as indicated in %) are as follows.

Table 4

The results shown in table 4 clearly indicate that the compositions A and B are far more efficacious than the marketed product.

Claims

1. Non-therapeutic use of a bipolar composite material comprising:

(ii) antimicrobial quaternary ammonium compound attached to a coordinating cation on one of said external surface planes, in an oral care composition to reduce dental hypersensitivity.

2. Use as claimed in claim 1 wherein said dental hypersensitivity is reduced by occlusion or blocking of dentinal tubules.

3. Use as claimed in claim 2 wherein said use brings about at least 70% occlusion or blocking of dentinal tubules as determined by dentine disc tubule occlusion method.

4. Use as claimed in claim 1 wherein said dental hypersensitivity is reduced by lowering the hydraulic conductance through dentine.

5. Use as claimed in claim 4 wherein hydraulic conductance is reduced by lowering the flow rate of fluid through the dentine.

6. Use as claimed in any of claims 1 to 5 wherein in said composite material, said antimicrobial quaternary ammonium compound is attached to coordinating cations on the external surface of the octahedral surface plane.

7. Use as claimed in any of claims 1 to 6 wherein when said precursor is an asymmetric 1:1 clay particle, said clay belongs to kaolinite or serpentine subgroup.

8. Use as claimed in any of claims 1 to 6 wherein, when said precursor is an asymmetric 2:1:1 clay particle, said clay belongs to chlorite subgroup.

9. Use as claimed in any of claims 1 to 8 wherein, in said composite material, the ratio of clay to said antimicrobial quaternary ammonium compound is from 1:0.001 to 1:1 parts by weight.

10. Use as claimed in any of claims 1 to 9 wherein median diameter (D50) of said composite material is 0.1 to 10 pm.

11. Use as claimed in any of claims 1 to 10 wherein said quaternary ammonium compound is one or more of cetylpyridinium chloride (CPC), cetyltrimethylammonium chloride (CTAC), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride (BKC), benzethonium chloride, cetrimide, quaternium, tetrabutyl ammonium bromide, undecylenamido propyltrimonium methosulphate, methylbenzethonium chloride, cetethyldimonium bromide, cetromonium tosylate, cocotrimonium chloride, dodecylbenzyltrimonium chloride, lauryl isoquinolium bromide, laurylpyridinium chloride, dequalinium chloride or domiphen bromide.

12. Use as claimed in any of claims 1 to 11 wherein said oral care composition comprises 0.1 to 10 wt % of said bipolar composite material.

13. Use as claimed in any of claims 1 to 12 wherein said oral care composition is a toothpaste.

14. Use as claimed in claim 13 wherein said toothpaste comprises calcium-based abrasive.

15. A bipolar composite material for use in an oral care composition in the treatment of dental hypersensitivity, comprising:

(ii) antimicrobial ammonium compound attached to a coordinating cation on one of said external surface planes,