WO2000059460A1 - Additives for desensitizing and remineralizing dentifrice compositions - Google Patents

Abstract

A composition and method for desensitizing and remineralizing dentinal and/or enamel surfaces comprises contacting a dentinal surface with inorganic oxide particles which principally have submicron median particle size, but can have a median particle size in the range of 0.05 to 3 microns. The particles are preferably porous and have a porosity of at least 0.5 cc/g when measured from a dried dispersion of the inorganic oxide particles. The composition can be applied as an aqueous or water miscible dispersion of particles. The particles can also be included in a conventional dentifrice paste containing conventional inorganic oxide abrasives. Silica gel and precipitated silica are examples of particularly suitable inorganic oxide materials for this invention.

Description

ADDITIVES FOR DESENSITIZING AND REMLNERALIZLNG DENTIFRICE COMPOSITIONS

BACKGROUND OF THE INVENTION

This invention relates to inorganic oxide-based dentifrice additives having particle sizes that promote their deposition and retention on and within hard (enamel) and soft (dentin) oral tissues.

Two areas of cm rent inteiest to the oral care industry are tooth sensitivity and remineralization phenomena. Tooth oi "dentinal hypei sensitivity" is defined as acute, localized pain in response to thermal, osmotic, tactile oi air blast stimulation of exposed dentin The hydrodynamic theory is the most widely accepted explanation for dentinal sensitivity. The mechanism for this phenomena is believed to stem from flow changes in open/exposed (i.e., to the oral environment) dentin tubules (which occurs frequently with gingival recession) which mechanically stimulates nerve receptors located at the dentin-pulp junction. Remineralization is a process in which calcium and phosphate are reintroduced into legions of the dentin and enamel that have reduced mineral content (i.e., deminerahzation). Reduced mineral content is typical in areas where caries and tooth decay are present. Microcracks and fissures in enamel/and or dentin surfaces can act as pathways for acidic oral fluid that contributes to canes development and weakened enamel.

Two established approaches to alleviate or reduce dentinal hypersensitivity are via 1 ) tubulai blockage and/oi 2) use of chemical agents to leduce sensory pulpal nerve activity. Credence to the effectiveness of the tubular blockage approach has been developed clinically by the use of high fluoride content topical treatment. Fluoride reacts with soluble calcium in the tubular fluids to precipitate very insoluble calcium fluoride. Such high fluoride content dentifrices are sold and recommended generally for professional use While effective, they have the very undesirable side effect of biownish tooth staining Professional topical agents which contain oxalate - -

also are available and have been shown highly effective in in vitro testing The disadvantages associated with that type of topical agent is its poisonous nature and need to be professionally applied

The second approach is one that is now commercially practiced. A number of dentifrices are marketed to provide relief from the discomfort associated with dentinal hypersensitivity The inclusion of potassium and to a lessei degree strontium salts in dentifrice compositions is a typical formulating approach Potassium nitrate is most commonly employed, but it is the K⁺ ion that in effect reduces the excitability of nerves at the pulp-dentinal junction Fluid movements in the tubules act as poweiful excitei s of nerve activity It has been shown by in vitro testing that the lole of potassium in the treatment of dentin itself is that of a modulator of nei ve excitability whereas hydraulic conductance testing shows its efficacy is foi tubulai blockage

A commeicially used approach to fostei leminerahzation involves the addition of adding soluble calcium and phosphate to a dentifπce in ordei to increase the concentrations of calcium and phosphate above ambient oral fluid levels during brushing Calcium phosphate precipitates fiom these treatments, and ultimately crystallizes and foims hydroxyapatite

SUMMARY OF THE INVENTION This cui rent invention is focused on the tubulai blockage mechanism and is the lesult of discovering and developing materials which aie paiticularly effective for reducing dentinal fluid flows through the deposition of said matenals on and within the dentin s uctuie. It has been found that paiticular inorganic oxide materials, when leduced to, e.g., submicron particle sizes, which are much smaller with a far greatei population of such particles than employed in commercially available dentifrice compositions, have the ability to deposit and be retained on and within the dentin structure This results in blockage of tubulai openings which i educes the degree of luid flow that can occui due to external stimuli such as air blast and/or temperature changes These principally submicron matenals, e.g., silica gels and precipitates, aie chemically compatible with the ingiedients typically foimulated into commercial dentifrice matenals Fuithermore, they can be used in conjunction with materials such as potassium nitrate that aie employed in desensitizing paste and gel type dentifrice foimulations These matenals can be fuithei modified with chemical components such as calcium and/oi phosphate that aie well known as being beneficial foi leminerahzation of oial tissues These materials can be fuithei combined with othei components such as polyunylmethyl ethei/maleic acid (PVM/MA) copolymeis that have been shown to have some effectiveness foi dentinal tubulai blockage

The above benefits aie specifically obtained by contacting porous dentinal surfaces with a composition compiising poious inorganic oxide pai tides, wheiein the particles have a median paiticle size in the lange of 0 05 to about 3 microns The particles of the invention also have poiosity such that when an aqueous dispeision of the pai tides is dried at least about 0 5 cc/g ol poie volume as measuied by BJH mtiogen poiosimetiy is fiom poies having a poie size oi 600A oi smallei Silica particles, and especially piecipitated silica and silica gel pai tides aie pielerred Especially pieferred pai tides have a median paiticle size in the range of 0 05 to about 1 micion The composition can be in the foim of a dispeision oi sluny of the pai tides, oi in the form of a conventional dentifπce

BRIEF DESCRIPTION OF THE DRAWINGS

Figuie 1 illustrates the diffusion test cell foi dentin disks Figuie 2 illustiates the appaiatus foi testing hydiauhc conductance

Figuie 3 illusti tes a blushing machine and closei pei spective of the test cell illustrated in Figuie 1

Figuie 4 illustrates the particle size distribution of a feed dispeision used to make the invention Figuie 5 illustrates the paiticle size distπbution of the feed dispeision in Figure

4 aftei the feed dispei sion has been milled

Figuie 6 illustiates the paiticle size distπbution of a dispeision accoiding to the invention which was piepaied by centπfuging the dispeision of Figure 5

Figure 7 illustrates the paiticle size distπbution of anothei feed dispersion used to make the invention Figure 8 illustrates the particle size distribution of the feed dispersion in Figure 7 after that dispersion has been milled.

Figure 9 illustrates the particle size distπbution oi a dispersion according to this invention which was prepared by centπfuging the dispersion of Figure 8 Figure 10 is a low magnification scanning electron micrograph (SEM) of dental surfaces (dental disk) which have been treated with the invention, as well as surfaces which have been untreated.

Figure 1 1 is a SEM/EDS representation of surfaces treated with invention.

Figure 12 is a graph of — versus mass traction solids ioi several inorganic

1 oxide materials suitable ioi this invention η is the viscosity of the dispeisions illustrated and η_{) is the viscosity of water The matenals illustrated weie milled and centπfuged according to techniques described herein

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS ( 1 ) Parent Inorganic Oxide Particles

Inorganic oxides suitable tor piepaπng the invention include precipitated inorganic oxides and lnoigamc oxide gels These inorganic oxides are referred to herein as "parent inorganic oxides," "parent particles" oi "parent dispersions" Amorphous piecipitated silica and silica gels are particularly suitable parent inorganic oxides The dispersion can also be prepared from mixed inorganic oxides including

SιO₂»Al₂O , MgO»SιO₂«Al₂0^. Mixed inorganic oxides are prepared by conventional blending or cogelhng procedures.

In embodiments comprising gels, the dispersions are derived from porous inorganic oxide gels such as, but not limited to, gels comprising Sι0₂, Al₂O , AlPOα, MgO, Tι0₂, and Zι0₂ Calcium phosphate gels are also suitable The gels can be hydrogels, aerogels, or xerogels. A hydrogel is also known as an aquagel which is formed in water and as a result its pores are filled with water. A xerogel is a hydrogel with the water removed An aerogel is a type of xeiogel from which the liquid has been removed in such a way as to minimize any collapse or change in the gel's structure as the watei is lemoved Silica gels commercially available as Syloid® grade gels, e.g., grades 74, 221 , 234, 244, W300, W500 and Genesis ^{1 M} silica gels are suitable parent inorganic oxides

Gels are well known in the ait. See Ilei's "The Chemistry of Silica", p. 462 ( 1979). Gel, e.g. silica gel, particles aie distinguishable from colloidal silica oi precipitated silica particles. For example, colloidal silica is piepared as a slurry of dense, non-porous silica particles. Colloidal silica particles typically are smaller than 200nm (0.2 micron). As mentioned earlier, these particles do not have internal porosity. On the other hand, typical dispersed precipitated particles have some internal poiosity In some cases, the internal porosity in typically precipitated particles, however, largely collapse undei capillary piessure cieated by receding menisci of water as the water evaporates during drying The conditions for making colloidal silica and precipitated silica are well known.

Gels, on the other hand, are prepared under conditions which promote coalescence of primary particles (typically having median particles sizes of 1 to l Onm, as measured under transmission electron microscopy, i.e., TEM) to form a relatively ngid three dimensional network The coalescence of gel is exhibited on a macioscale when a dispersion of inorganic oxide, e g., silica, hardens to a "gel" oi "gelled" mass having structural integrity

Methods of preparing inorganic oxide gels are well known in the art. For example, a silica gel is prepared by mixing an aqueous solution of an alkali metal silicate (e.g , sodium silicate) with a strong acid such as nitric or sulfuπc acid, the mixing being done undei suitable conditions of agitation to form a clear silica sol which sets into a hydrogel, i.e , maciogel, in less than about one-half hour. The lesulting gel is then washed. The concentration of inorganic oxide, i.e., Sι0₂, iormed in the hydrogel is usually in the range of about 10 and about 50, preferably between about 20 and about 35, and most preferably between about 30 and about 35 weight percent, with the pH of that gel being from about 1 to about 9, preferably 1 to about 4. A wide range oi mixing temperatuies can be employed, this range being typically from about 20 to about 50°C The newly formed hydrogels are washed simply by immersion in a continuously moving stream of watei which leaches out the undesirable salts, leaving about 99.5 weight percent or more pure inorganic oxide behind

The pH, temperature, and duration of the wash water will influence the physical properties of the silica, such as surface area (SA) and pore volume (PV)

Silica gel washed at 65-90°C at pH's of 8-9 for 15-36 houis will usually have SA's of 250-400 and form aerogels with PV's of 1 4 to 1 7 cc/gm. Silica gel washed at pH's of 3-5 at 50-65°C for 15-25 hours will have SA's of 700-850 and form aerogels with PV's of 0 6- 1.3 These measurements are generated by N₂ poiosity analysis Methods for preparing inorganic oxide gels such as alumina and mixed inorganic oxide gels such as silica/alumina cogels aie also well known in the ait. Methods for preparing such gels aie disclosed in U S Patents 4,226,743, the contents oi which are incorporated by reference.

In general, alumina gels are prepared by mixing alkali metal aluminates and aluminum sulfate Cogels aie prepared by cogellmg two metal oxides so that the gels are composited togethei. For example, silica alumina cogels can be prepared by gelling an alkali metal silicate with an acid or acid salt, and then adding alkali metal aluminate, aging the mixture and subsequently adding aluminum sulfate The gel is then washed using conventional techniques Another embodiment of this invention is derived irom dispersions of ceitain piecipitated inorganic oxides. For example, milling certain precipitated silicas results in dispersions having the porosity properties described latei below

Reinforced precipitated silica such as that described in U.S. Patent 4, 157,920 can also be used to prepare the dispersion of this invention The contents of that patent are incorporated herein by reference Foi example, reinfoiced precipitated silicas can be prepared by fust acidulating an alkali inoiganic silicate to create an initial precipitate. The lesulting piecipitate is then leinfoiced or "post conditioned" by additional silicate and acid The piecipitate lesulting from the second addition of silicate and acid comprises 10 to 70% by weight of the precipitate initially prepared. It is believed that the leinforced structure of this piecipitate is moie rigid than conventional precipitates as a result of the second precipitation It is believed that even after milling, centπfuging and subsequent drying, the reinforced silicate substantially maintains its netwoik rigidity and poiosity. This is in contrast to othei precipitated silicas such as those disclosed in U.S Patent 5,030,286. Other suitable inorganic oxides include amorphous silica derived from natural occurring deposits such as diatomaceous earth and biogenic silicas such as that prepared from rice hulls.

Once an inorganic oxide is selected for the parent dispersion, a liquid phase of the selected inoiganic oxide is prepared The medium foi the liquid phase can be aqueous oi some other medium These othei mediums include watei miscible liquids in which the final dispeision is used. These mediums are described latei on The liquid phase, for example, can be residual water in inorganic oxide gels which have been drained, but not yet dried, and to which additional water is added to reslurry the gel. In another embodiment, dried inorganic oxides, e.g., xerogels, are dispersed in liquid medium.

In genei al, the parent dispersion should be in a state that can be wet milled. In most embodiments, the pai ent dispersion has a median particle size approximately in the uinge of 10 to 40 microns However, the size of the parent particles only needs to be sufficient such that the mill being used can produce a dispersion having the desired median particle size at about or below 3 microns. In embodiments prepared from a drained inorganic oxide gel. the drained gel may first be broken up into gel chunks and premilled to produce a dispersion of particles in the range of 10 to 40 microns.

(2) Milling The parent dispersion is then milled. The milling is conducted "wet", i.e., in liquid media. The general milling conditions can vary depending on the feed material, residence time, impeller speeds, and milling media particle size. Suitable conditions and residence times are described in the Examples. These conditions can be varied to obtain the desired size within the range of 0.05 to about 3 microns The techniques for selecting and modifying these conditions to obtain the desired dispersions are known to those skilled in the art The milling equipment used to mill the parent inorganic oxide particles should be oi the type capable of severely milling and reducing matenals to particles having sizes about three microns or smaller, particularly below one micron, e.g., through mechanical action. Such mills are commercially available, with hammer and sand mills being particularly suitable for this purpose. Hammer mills impart the necessary mechanical action through high speed metal blades, and sand mills impart the action through rapidly churning media such as zuconia or sand beads Impact mills can also be used Both impact mills and hammei mills reduce paiticle size by impact of the inorganic oxide with metal blades A dispeision compπsing particles of thiee micions or smallei is then tecovered as the final pioduct

Further processing of the dispersion may also be needed to insure that essentially all of the distribution of particles is below about two microns and especially when dispersions in the size range of 1 micron or less is desired. In such a case, the milled dispersion is processed to separate the dispersion into a supernatant phase, which comprises the pai tides oi the final product, and a settled phase which comprises the larger particles The separation can be created by centπtuging the milled inorganic oxide particles. The supernatant phase is then removed from the settled phase, e.g., by decanting The supernatant is the dispersion of this invention Conventional centrifuges can be used for this phase separation. In some instances, it may be pieferable to centrifuge the supernatant two, three or moie times to fuithei remove large particles remaining after the initial centrifuge. It is also contemplated that the laigei particles of a milled dispersion can separate ovei time under normal gi avity conditions, and the supernatant can be removed by decanting.

Depending on the product particle size targets, the settled phase also can be regarded as the particles of this invention. For example, if a dispersion of larger particles within the range of 0 05 to 3 microns are desued, the settled phase can be removed and ledispersed. In such instances, the paient dispersion may need to be milled more than once to insuie that the settled phase has the appropriate particle size in the range of 0.05 to 3 micions The dispersion oi particles also can be modified after milling to insure a stable dispeision. This can be accomplished through pH adjustment, e.g., adding alkaline material, 01 by the addition of conventional dispersants The dispersions can also be stabilized in certain instances by employing water miscible liquids as the dispersing medium or exchange the water with a water miscible liquid.

(3) Inorganic Oxide Dispersion

As indicated earhei , the median particle size, i.e , particle diametei . of the particles in the dispersion is in the l ange of 0 05 to about 3 microns The size is pπmaπly dictated by the dispersion's use and can be in ranges of, e g . between 0 06 to 2 9, 0 07 to 2 8, and so on The median particle size is measuied using conventional light scattering instrumentation and methods The sizes lepoi ted in the Examples were determined by a LA900 lasei scattering particle size analyzei from Hoπba Instruments, Inc

The solids content of the dispersion vanes The solids content of the dispersion can be in the l ange of 1 -30% by weight, and all l anges in between It also may be as low as 0.5% by weight A solids content in the l ange of 10 to 20% by weight is suitable foi a number of applications

In general, the dispeision's viscosity should be such that the dispersion is a pumpable liquid The viscosity of the dispersion is highly dependent upon the dispersion's solids content and the poiosity of the particles The viscosity of the dispersion's liquid phase and the completeness of the dispersion can also affect the oveiall dispersion

Embodiments prepared from silica gel genei ally have viscosities similai to the viscosities of the parent silica dispersion. Foi example, when paient silica gel is milled at a pi escribed pH in the range of 9- 10, e.g , 9 5, the viscosity of the milled silica lemains lelatively unchanged This is distinguishable from viscosities oi milled precipitated silicas The viscosities of milled piecipitated silica are less than the viscosity oi the paient material

The pH of the dispersion depends upon the inorganic oxide and additives used to stabilize the dispersion The pH can be in the l ange of 2 to 1 1 . and all ranges in between For example, dispersions of alumina geneially have a pH in the range of 2 to 6 Silica dispersions aie genei ally neutial to modeiately alkaline, e g , 7 to 1 1 The pH can also be modif ied using conventional pH modifiei s

With lespect to embodiments compiising silica gel, the dispei sion is lelatively fiee of impui ities when compared to embodiments compi ising, foi example, piecipitated inoiganic oxide particles Paient silica gels are typically washed to lemove substantially all impurities The alkali salt content of gels are typically as low as 100 ppm by weight and generally no more than 0 1 % based on the weight of gel The low impurity levels of silica gels aie especially advantageous when colloidally stable dispei sions oi pai tides aie desn ed The poie volume of the pai tides in dispei sion can be measuied by mtiogen poi osnneti y aftei the dispei sion is dπed In genei al, at least about 0 5 cc/g of the pai tides poie volume is fiom poies having a poie size of 600A of less Theie are embodiments comprising silica gel in which at least 0 7 cc/g and 0 9 cc/g of pore volume fiom pores having sizes less than 600A In those embodiments, up to 100% of the poies have diametei s less than 600A, and at least at least 80% and up to 100% of the poies silica gels have diametei s of 300 A oi less The total poie volume of the dπed dispei sions is in the lange of about 0 5 to about 2 0 cc/g, with embodiments comprising silica gel having total poie volume measuiements in the l ange of about 0 5 to about 1 5, and foi ceitain silica gel embodiments in the lange of about 0 7 to about 1 2 cc/g The pore volume for the dried dispersion has been pH adjusted and is measured using BJH mtiogen poiosimeti y aftei the dispei sion has been pH adjusted, slowly dπed at 105°C foi at least sixteen houis and activated at 350°C foi two houi s undei vacuum

As mentioned eaihei, the poiosity of the pai tides piovides a mechanism foi cairying additional beneficial additives conventionally used in dental and oial caie pioducts Indeed, the porosity in silica gel embodiments provide a pioduct having a consistent pore volume that does not leadily collapse

In addition to measuring poiosity fi om dπed dispei sions, the poiosity of the pai tides in this invention can also be def ined as a viscosity deπved poi e volume Figuie 12 shows that as loadings of poious paiticles incieases, viscosity (r] )ιncιeases in such a manner that a linear relationship is obtained when — - is plotted against a η certain range of particle loadings. 77₀ is the viscosity of the dispersion's solvent, i.e., water. As shown in Figure 12, slope for the curve shown increases as the porosity of particles increases. A "viscosity derived pore volume" for the inventive particles thus can be calculated from the slope of these curves. These values reflect pore volumes for the dispersed particles.

For example, the effect of loading small particles on the viscosity of a dispersion of those particles in a Newtonian fluid is described by I.M. Krieger in Adv-

^*n

Coll. Interface Sci., 1972, 3, 1 1 1 . The formula defines the reciprocal of — - with the

■1 following formula ( 1 ).

-ah

Φ

( I )

*7o ^"b . wherein η is the dispersion's viscosity

77₀ is the viscosity of the fluid in which the particles are dispersed Φ is the volume fraction of the suspension occupied by the particles a is the "intrinsic viscosity" (equal to 2.5 for spherical, or very low aspect ratio, uncharged particles) b is the volume fraction at which the viscosity becomes infinite.

A relationship (2) also exists between Φ and the mass loading (A-) of particles in the suspension expressed as a mass fraction, and the particles skeletal density

(p.v) and its apparent pore volume (PVa) , referred to herein as the "viscosity derived pore volume".

where pf is the density of the fluid phase

η_Q Coupling of equations ( 1 ) and (2) yields a relationship relating — to the mass

loading of particles For relatively small values of x this relationship can be illustrated by the following hneai expression which is independent of the parameter b

— = 1 - a[ pf + PVa (3) ps η This hneai relationship generally holds for values of — from 0.5 to 1.0. η

Viscosity data foi a system of well dispersed particles can then be plotted in the form

Tl 7] of — ( x) and linear regiession applied to the — - data of 0.5 to 1 .0 to deteimine the η - η slope. From equation (3), it is appaient that this slope can be related to the PVa of the particles by the following equations

1 > slope = —a[ pf — + PVa (4) s J

Knowing the skeletal density of amorphous silica (2. 1 g/cc), the density of the fluid phase (water = 1 .0 g/cc) and knowing that the intrinsic viscosity, a, is equal to approximately 2.5, PVa for the invention is calculated. This curve is illustrated in Figure 12 foi sevei al embodiments of the invention, as well as a lelatively non-poious colloid The viscosity derived pore volume values foi dispei sions. especially dispersions of silica, are, in general, determined accoiding to the following methodology - - -

( 1 ) A dispersion of selected inorganic oxide is milled at one liter per minute and centπfuged for thirty minutes at 600 g or at 2,000 g.

(2) The pH oi the sluπ y is then adjusted so that a good dispersion is obtained and maintained. Typically this is obtained by adjusting the pH of the dispersion away from the lsoelectπc point of the particles, but not into pH regimes that would cause excessive dissolution of the particles (e.g., for silica adjust the pH to between 9.7 and 10.3 by adding NaOH). In general, this pH range of optimum dispersion can be determined by titration of a 5 wt.% solids dispersion through the entire region of acceptably low particle solubility and determining the pH range associated with minimum dispersion viscosity The milled dispersion from ( 1 ) is then adjusted to a pH in that range

(3) The viscosity (η) of the dispersion is measuied and the viscosity of the dispersion's medium \T ₀) , e.g., water, is determined. These viscosities are measured using a Brookfield viscometei at 74 sec ' at 25.0 ± 0. 1 ° C η ?],, , . (4) The ratio of — is then detei mined to obtain — ) values uniformly

7 ₀ dispersed thiough the l ange of — values between 0.5 and 1 .0. This is accomplished η by first estimating the slope of — -(x) using a reference sample and then using that

estimated slope to determine the concentration of dispersions to be prepared to give

^0 ⁷7<> the desired range of — determinations. If — of the dispersion from (2) is greater 77 77 than 0.5 and less than 0.9 it can be used as the reference sample to calculate the η₍₎ . 77₀ estimated slope. ESL, for the — ( x) plot. If — is less than 0.5, the dispersion sample η 77

In lo must be diluted with solvent (typically DI water) then reevaluated for — . If — is

77 77 greater than 0.9, a more concentrated dispersion sample must be obtained Once a reference sample with — ⁷7o between 0.5 and 0.9 is obtained, the mass

Α loading (x) is determined using conventional techniques and ESL is calculated from the following equation.

(5) Concentrations x values) for a series of samples for the PVa determination are calculated using the following formulae.

t arget = — η

.9 - 1 ESL

8 - 1

.8 ESL

7 - 1

.7 A = ESL

.6 - 1 ESL

5 - 1

.5 λ = ESL

(6) Dispersions with these mass loadings are then prepared within the appropriate pH range determined in (2). (7) The viscosity of each of these samples is determined by Brookfield viscometer at a shear rate of 73.4 sec. ' after equilibration at 25.0 ± 1 ° C/ These data are then plotted (8) Regression analysis is applied to obtain the slope of the data generated, and

the slope, ps , and pf are input into the formula slope = -2.5 — + PVa f to ps calculate (PVa s)

Silica dispersions of this invention show curves having an absolute slope of about 2 40 or greater, and generally in the range of 2 4 to 10.0. This data generally translates into dispersions having viscosity deπved pore volumes (PVa' s) of at least about 0.5cc/g Pieferred embodiments have a slope in the range of 3 50 - 5.0 and prefeπed PVa % of about 1 0 to about 1 5 cc/g

The stability of the porosity in the dispersed particles of this invention is evidenced by calculating the loss in pore volume after the dispersion is dπed As stated eai hei , poiosity in aqueous dispersed pai tides comprising less rigid networks of primary particles can be significantly reduced as water evaporates from the dispersion Comparing the dispersion's PVa and the pore volume measured after the dispersion is dried shows that at least 40% of the PVa is maintained tor dispersions of this invention Ceitain embodiments show that at least about 60% of the pore volume is maintained.

The invention can comprise the dispersion as is pioduced by milling and centπfuging The slurry or dispersion can be aqueous or in some other medium. Suitable mediums include water miscible liquids such as those typically used to make dentifrice compositions Suitable mediums include sorbitol and glycerin

In general, the median particle size of the slurry or dispersion is in the iange of about 0 05 microns to about 3 microns, but can also be in the range of 0 05 to 2 microns or 0.05 to 1 micron Particulai embodiments described below have a median particle size in the range of 0.2 to 1 .0 micron or 0.2 to 0.8 micron, with a standard deviation in the range of 0.2 to 0 8 micron Indeed, substantially all of the particles employed for the invention, i.e , 99%, aie below 3 microns, preferably below 1 micron and with certain embodiments below 0.8 microns These pai ticle sizes are repoited in conventional volume-based statistics Without being held to a particular theory, it is believed that the pai ticle sizes of the invention are the same as oi smaller than the diameters of the tubular openings on the dentinal surface. Those openings as measured by SEM are typically two microns or smaller. It is believed that the invention affects desensitization as a result of tubular blockage by virtue of the principally submicron size of the particles which allows them to enter and be retained therein. The resultant diminished dentinal flows upon exposure to temperatuie changes and other external stimuli is reflected by a reduction in pain commonly associated with sensitive teeth

Without being held to a particular theory, it is believed that at effective amounts, the particles of the invention deposit and otherwise become anchored to the surfaces of the enamel and dentin fissures and microcracks mentioned earlier. The inorganic particles can then act as a host foi calcium phosphate precipitation and subsequent crystallization and formation of hydroxyapatite

As mentioned earlier, the solids content of the dispersion can be in the l ange of 0.5 to 30% by weight. Howevei , the solids content can vai y depending on the medium in which the particles are dispersed and the viscosity desired for the dispersion. The solids content also depends on the amounts of inorganic oxide needed to effect desensitization and/or remineralization.

In certain embodiments, calcium and/or phosphate can be combined with, oi incorporated into inoiganic oxide particles of this invention to enhance remineralization as a result of calcium phosphate piecipitation it the site of deposition oi said inoi ganic oxide particles. As mentioned eai liei , calcium phosphate piecipitates further ci ystalhze to form hyαroxyapatite which can fill fissures and microcracks in dentin and enamel surfaces The calcium and/or phosphate can be added by co-milling calcium and/or phosphate salts along with the inorganic oxide, or in a specific embodiment co-milling amorphous forms of calcium and/or phosphate The calcium and/or phosphate can also be mixed with the dispei sion oi inorganic oxide pai tides after the particles have been milled and centπf uged Adding calcium and/or phosphate to the porous pai tides oi the invention allows the calcium and/oi phosphate to be incorporated within the porous structui e of the particles Then, upon deposition of the invention onto and/or within the dentinal tubular openings, the calcium and/or phosphate are delivered to and undergo piecipitation at the same site Upon calcium phosphate precipitation, there is subsequent foimation of hydroxyapatite at those dentinal sites that have reduced mineial content

The aforementioned dispersion of inorganic pai tides also can be added to a conventional dentifrice formulation to foim anothei embodiment of the invention

Conventional dentifrice foimulations comprise humectants, abrasives, and additives such as flavors, anti-canes additives and the like Additional examples of dental additives aie potassium nitrate and strontium chloride added for desensitization Examples of anti-microbial agents aie tπclosan, cetylpyπdinium chloride (CPC), chlorhexidene, 13G (aldyl dimethyl betamine, dimethyl alkylamine oxide, sodium fluoride) and methyl paiaben Othei examples of anti-miciobial agents include metal salts such as zinc Examples of a vaπety of specific ingiedients typically included foi promoting dental hygiene aie sodium fluoπde, stannous fluoπde, sodium monof luorophosphate, calcium salts, phosphate salts, pyrophosphates, and sodium citrate All of the additives above can be combined using conventional techniques

The particles can be added to the dentifrice as a dispersion prepared using the methods above. The pai tides of the afoiementioned dispeision can be added so that the pai tides are a pait of oi in addition to any inoiganic abi asives employed in the dentifi ice Dental abrasives typically have median pai tides sizes in the l ange of 8-20 microns and geneially make up 10 to 30% by weight of the dentifi ice The lemaimng balance of the dentifrice comprises humectants such as soi bitol oi glycerin, tieatment additives such as the vaπous forms of fluoride, colorants, and the like Geneially, the aforementioned dispersion would be added so that the particles of the dispersion is a distinct portion of the dentifiice which comprises 0 5 to about 15% by weight of the dentifi ice

Indeed, a dentifi ice accoiding to this invention comprises a population of particles which is believed to be unique compaied to conventional abiasive-containing dentifπces In particular the dentifrice of this invention comprises 0 5 to 15% by weight of poious inorganic particles having a median particle size in the range of 0.05 to 3 microns Moie prefeiably, the dentifπce comprises 2- 10% by weight of porous inoi ganic pai tides having a median particle size in the tange of 0 05 to 2 micions, and even more preferably a median particle size of 0.5 to 1.0 micron. As mentioned earlier, the size of particles per this invention can also be characterized as preferably having a mean particle size in the range of 0.2 to 1.0 micron and having a standard deviation in the range of 0.2 to 0.8 micron The pH of the dentifrice would be that of conventional dentifrices and could be different over the pH of the invention compπsing the dispeision per se Foi example, the pH of typical dentifπces, e.g., a toothpaste, would usually be in the pH range of 6-8 The dispersion per se would be more in the range of 8- 10 and could be modified just prior to use to have a pH in the range of 5.5 to 8 This modification could be effected by mixing the dispersion with a pH modifying component

Indeed, ceitain embodiments oi the invention comprise a two pai t treatment package One pai t comprises the dispei sion pei se and the other comprises a pH modifier such as monobasic potassium phosphate oi monobasic sodium phosphate When the treatment is applied, the two components are mixed to produce a composition having a relatively neutral pH The pH modifiei is selected to modify the pH of the invention in order to produce a product which is safe, e.g., neutral, foi contact with oral tissue, as well as produce a compatible environment for other oral caie additives, such as fluoride

EXAMPLES

In order to measure the effectiveness of vaπous materials and dentifrice compositions of the invention for reducing dentinal fluid flows, sample preparation, equipment, treatment protocols, and test methods similar to those reported in the journal hteratuie weie established as described in this example

Dentinal Sample Preparation

Human molars (typically unerupted thud molars) are used as sources of dentin foi in vitro flow measuiement commonly iefeπed to as hydraulic conductance testing Disks of approximately 0 7- 1 millimeter in thickness are prepared by cutting the tooth using a saw (such as a Buehler Isomet low speed saw) with diamond containing wafeπng blade To prepaie teeth foi cutting, the occlusal suiface (ci own side) of a selected (based on coloi , lack of obvious caries or fillings) tooth is bonded using a commercial epoxy resin system to a short length of aluminum lod The aluminum rod serves to provide a secure mount in the saw The fust cut is made parallel to the occlusal suiface and lemoves the root Ideally that cut will be at the pulp-dentin junction with the pulp removed by saw keif. If any pulp is observed to be piesent, it will be sanded off using fine grit silicon carbide papei The second cut will at the enamel-dentin junction ideally with all the enamel removed by the saw kerf Again should there be in this case enamel lemaimng after this cut, this side will also be sanded. The ideal specimen contains neithei enamel noi pulp on the dentin surfaces The resultant specimen will hereaitei be leferied to as a dentin disk

Dentinal Sample Conditioning

When the dentin disks are prepared via such cutting and sanding operations discussed previously, it has been well established in the journal literature that theie is the development of what is termed a smeai layer The smeai layei is basically the cutting and sanding debris that remains on the dentin sin faces This smeai layei causes plugging of at least some of the tubulai openings which manifests itself in leduced fluid flows compared to the possible fluid flows with all the tubules open Most common piactice in studying the effect of materials on tubular blockage is to remove the smeai layer before such testing This is typically accomplished by acid etching. Phosphoric, boric and citric acids are commonly used for smear layei removal In the examples to be described in this disclosuie, a 15 second etch with 37% phosphoric acid, followed by copious flush with watei is employed as a standard smeai layei lemoval tieatment

Hydraulic Conductance Testing

Hydraulic conductance testing measures the rate of fluid flow thiough the dentin disks prepared and conditioned as discussed above. The key equipment used to test the late of fluid flow through dentin specimens, specifically dentin disks is the same as that reported in the journal hteratuie and is what is commonly known as a

Pashley permeability test cell (puichased commercially from Kenward Company oi North Augusta, South Caiohna). The conditioned dentin disk is mounted in the test cell (see Figuie 1 ) in such an orientation that the flow direction will be through (in) the pulp side of the disk to (out) the crown side of the disk. That orientation is used for all testing to be described herein. Distilled water is used as the test fluid in the examples to follow. Ten psig of fluid pressure is applied to the test cell. The flow rate is determined by measuring the linear movement of a bubble in a capillary tube of established volume/length ratio (both 25μl/65mm and 100μl/ l 15mm capillaries sizes are used) See Figure 2 for photo of test equipment. Hydraulic conductance is defined as the volume flow rate pei unit time per unit cross-sectional flow area pei unit hydiostatic water pressuie One cell configuration of constant cioss-sectional area is employed in all the examples which follow, the units of measure will only be reported as microliters per minute per cm of watei pei squaie centimetei (cm) oi cross-sectional area The nominal cross-sectional flow area is 0 157cm^" Because dentin is variable from tooth to tooth, lephcate testing is conducted with each dentin specimen used as its own control. Multiple readings aie taken aftei each specific treatment

Test Protocol:

Hydraulic conductance testing measures how the flow characteristics vary as the dentin disks aie treated with matenals (e g., silica slui πes, toothpaste) of varying properties (chemical as well as physical) A test routine was established which in general is mentioned thioughout this disclosure. The general treatment routine is as follows:

Based on nominal ID (0 176" ) ol a numbci 008 si/c o-πng Actual ai ea may be si lghtly less due to compi ession ot o-πng

The brushing opeiation discussed above is conducted without removal of the dentin disk from the permeability test cell Brushing is earned out foi the pi escribed time using a biush fabπcated from a Butlei End Tuft biush model number 307 soft Blushing is done with a circulai motion at 140 Rpm The blushing apparatus is shown in Figuie 3

Post-moitem examination of the dentinal test specimen In addition to measuπng the magnitude of hydiaulic conductance leduction due to treatment with vaπous materials, equally important is the understanding how the dentin fluid flows are affected by treatments with materials of vaiying properties This has been achieved by examining the samples aftei hydi aulic conductance testing via techniques such as Scanning Election Mici oscopy (SEM) and Energy Dispei sive Specti oscopy (EDS) This allows one to ldate the changes in hydi aulic conductance with changes in the suiiace and stiuctuie of the dentin Specifically, those analytical tests allow one to visualize how and wheie the tieatment mateπal(s) have deposited on the surface oi within the tubular openings Preparation of the dentin specimens foi those analytical techniques usually (depending on the specific type of analytical - - -

device) requires the samples to be dried. Where drying was carried out, it was done so in vacuo at ambient temperature. Once dried the dentin disks are prepared and examined via conventional SEM and EDS imaging techniques. Care is taken to be certain that the orientation (that is, the pulpal and occlusal sides) can be related to the side that has been exposed directly to the treatment materials.

Example 1 This example describes preparing an embodiment of this invention from a silica gel. Furthermore, the submicron particles of silica produced are sufficiently small enough to penetrate into the tubular openings.

A commercially available silica gel powder known as Syloid® W500 was used as the silica source in preparing the submicron silica dispersion. Syloid W500 has a solids content of 47% by weight as measured using an Ohaus moisture determination balance model 6010. Particle size distribution measured using a Horiba LA900 laser diffraction analyzer is shown in Figure 4 which shows the absence of submicron particles. Median particle size is 7.64 microns (measured after 2 minutes ultrasonication). A 20% solids slurry was prepared by high shear dispersing 1063.8 gra s Syloid W500 into 1436.2 grams deionized water. The resultant slurry was introduced into a Netzsch LabStar Type LS- 1 Zeta media mill. The silica slurry was milled for 45 minutes producing a slurry with reduced particle size as shown in Figure

5. This slurry was then centrifuged on a Dupont Sorvall RC-5B Superspeed Centrifuge with a type HS-4 swing bucket at 5000 Rpm for 60 minutes after which the liquid layer containing the submicron product was separated from the centrifugate. The separated submicron dispersion had a particle size distribution as shown in Figure 6, had a median particle size of 0.23 microns, had a solids content of 47% as measured via Ohaus, and had a pH of 9.06. From this dispersion two series of test samples were prepared. Because the samples were targeted for use in vivo clinical trials, as well as in vitro testing, a large number of one-time use vials were filled with aliquots. One set of samples was prepared by diluting that dispersion with deionized water to 8% silica solids. And another set was transferred to vials at full strength.

That latter set would be combined with a prescribed amount of monobasic potassium phosphate solution contained in separate vials to result in a near neutral pH and 8% silica solids content These three sets of vials (dispersion at 8% solids and pH ~ 9 to be known as Example 1 B-S, dispersion at 12% solids and pH ~ 9 to be known as Example 1 A-S, and monobasic potassium phosphate solution to be known as Example 1 P-S). These sample vials were autoclaved at 230°F for 15 minutes to render the contents sterile. The samples were ready for use at this point.

Example 2 The example descπbes the pieparation of anothei submicron silica dispeision that exhibits effectiveness for reducing dentin fluid flows

A size reduced silica hydrogel was used as the silica source in preparing submicron silica gel dispersions for this example. The silica gel has a solids content oi 47.2% by weight as measured using an Ohaus moisture determination balance model 6010 Particle size distribution measured using a Horiba LA900 lasei diffi action analyzei is shown in Figuie 7 Median particle size is 8.89 microns

(measured aftei 2 minutes ultrasonication) A 20% solids slurry was prepared by high sheai dispersing 1059.3 grams of the silica gel into 1440.7 grams deionized watei The resultant slurry was introduced to a Netzsch LabStai Type LS- 1 Zeta media mill. The silica slurry was milled for 45 minutes producing a slurry with reduced particle size as shown in Figure 8 This slurry was then centrifuged at 5, 100 Rpm for 60 minutes after which the liquid layei containing the submicron product was separated from the centπfugate The separated submicron dispersion had a particle size distribution as shown in Figure 9. had a median particle size of 0.29 microns, had a solids content of 15% as measured via Ohaus, and a pH of 8.74. From this dispersion two series of test samples were prepared. Because the samples were targeted foi use in in vivo clinical trials, a large number of one-time use vials were prepared. One set of samples was prepared by diluting that dispersion with deionized water to 8% silica solids And another set was transteired to vials at full strength after having been adjusted to pH 10 using potassium hydroxide solution That latter set would be combined with a prescribed amount of monobasic potassium phosphate solution contained in separate vials to result in a near neutral pH and 8% silica solids content These three sets of vials (dispeision at 8% solids and pH ~ 9 to be known as Example 2 B-S, dispersion at 13.79% solids and pH ~ 10 to be known as Example 2 A-S, and monobasic potassium phosphate solution to be known as Example 2 P-S) These sample vials were autoclaved at 230°F for 30 minutes to lender then sterile and microbiologically sate tot clinical use The samples weie ready foi use at this point

Example 3 Hydraulic conductance testing was caiπed out on three separate dentin disks employing the test protocol discussed eaihei . The data are summarized in Table I The silica dispersion identified as Example IB-S was used in the three test runs The data show this silica dispersion is quite effective foi I educing hydraulic conductance

Example 4 Hydraulic conductance testing was carried out on three separate dentin disks employing the test protocol as discussed eaihei The data aie summarized in Table 2

The silica dispersion identified as Example 1 A-S/ 1 P-S mix was used in the three test runs Freshly mixed dispersions weie employed foi each brushing tieatment The data show this silica dispeision is quite effective foi i educing hydiaulic conductance

Example 5

Hydraulic conductance testing was caiπed out on three separate dentin disks employing the test protocol as discussed earliet . The data are summarized in Table 3. The silica dispersion identified as Example 2A-S/2P-S mix was used in the three test runs Freshly mixed dispeisions weie employed foi each brushing treatment The data show this silica dispeision is quite effective foi l educing hydiaulic conductance

Example 6 To illustrate the ineffectiveness foi hydraulic conductance reduction, a silica (a silica source as used for dispersions piepared in Example 1 ) having a particle size typical of silicas employed as a dentifπce abrasive was dispei sed in deionized water to form an 8%> solids content sluπy This dispersion was then employed in the bl ushing treatments in triplicate testing of separate dentin disks. The data are summarized in Table 4. The data show treatment with conventionally sized silica is generally ineffective for reducing hydraulic conductance.

Example 7

To illustrate that the submicron silica of the invention has deposited and penetrated through the dentinal tubular openings, SEM data are shown in Figure 10 of the occlusal (side) surface which shows how the silica has coated the dentin where it has come in contact. The dentin disk had been removed from the test cell after run 19 (see Table 2) was completed. The dentin disk was vacuum dried at ambient temperature. SEM imaging of the pulpal (side) surface shown in Figure 1 1 indicates that the submicron silica has penetrated through the tubules. The presence of silica had been established via EDS analysis of selected areas on the pulpal side of the dentin disk which had not had direct contact with the silica dispersion.

A similar examination of a dentin disk after treatment with the conventional silica failed to show any evidence of silica on the pulpal side.

hters/min/cm H->0/cm

liters/mm/cm H-iO/cm

litcrs/min/cm H^O/cm

Claims

- -We claim:

1. A dentifrice composition compπsing fine sized porous inorganic oxide particles wherein: (a) said inorganic oxide particles have a median particle size of at least about 0.05 microns to about 3 microns, and (b) said inorganic oxide particles have a porosity of at least about 0.5 cc/g in pores of about 600 A or smaller.

2. The dentifrice composition of claim 1 wherein said porous inorganic oxide particles are present in amounts of about 0.5% to about 15% by weight of the dentifrice composition.

3. The dentifrice composition of claim 1 wherein said porous inorganic oxide particles comprise silica gel.

4. The dentifπce composition of claim 2 wherein said porous inorganic oxide particles comprise precipitated silica.

5. The dentifrice composition of claim 1 wherein said porous inorganic oxide particles are derived from naturally occurring siliceous minerals selected from the group consisting of feldspar, talc, pumice and diatomaceous earth.

6. The dentifrice composition of claim 1 wherein the porous inorganic oxide particles comprise silica gel having a median particle size in the range of about 0.05 micron to about 1 microns.

7. The dentifrice composition of claim 1 wherein the porous inorganic oxide particles comprise silica gel having a median particle size in the range of about 0.2 micron to about 0.8 micron. - - -

8. The dentifrice composition of claim 1 comprising about 2% to about 10% of said inorganic oxide particles based on total weight of the dentifrice composition.

9. The dentifrice composition of claim 1 having a pH in the range of about 5.5 to about 10.

10. The dentifrice composition of claim 1 further comprising humectant.

1 1. The dentifrice composition of claim 1 further comprising desensitizing additive.

12. The dentifrice composition of claim 1 1 wherein the desensitizing additive comprises potassium nitrate or strontium chloride.

13. The dentifrice composition of claim 1 further comprising calcium oxide.

14. The dentifrice composition of claim 1 further comprising calcium phosphate.

15. The dentifrice composition of claim 1 further comprising anti-gingivitis agent.

16. The dentifπce composition of claim 1 further comprising polyvinylmethyl ether/maleic acid copolymer.

17. The dentifrice composition of claim 1 further comprising additional inorganic oxide particles having a median particle size in the range of about 8 to about 20 microns.

18. The dentifrice composition of claim 1 further comprising stannous fluoride or potassium oxalate.

19. The dentifrice composition of claim 1 wherein the composition is in two or more parts, wherein one part comprises the inorganic oxide particles and a second part comprises calcium or phosphate salts. A method of tieating dentinal hypersensitivity and/oi effecting remineralization of dentinal and/oi enamel suifaces, the method compi ising applying to a dentinal suiface a composition compπsing tine size poious inorganic oxide pai tides wherein (a) said inorganic oxide paiticles have a median particle size in the lange of about

0 05 microns to about 3 microns, and (b) said inorganic oxide paiticles have a poiosity of at least about 0 5 cc/g in poies of about 600A oi smallet

The method wheiein said inoiganic oxide paiticles aie piesent in amounts of about 0 5% up to about 1 % by weight of the total composition

The method of claim 20 wherein said poi ous inoiganic oxide paiticles compπse silica gel

The method of claim 20 wheiein said poi ous inoiganic oxide pai ticles compπse piecipitated silica

The method of claim 20 wheiein said porous inorganic oxide particles aie denved fiom natuially occurring siliceous minei als selected fiom the gioup consisting oi feldspai , talc, pumice and diatomaceous eai th

The method of claim 20 wheiein said poious inoi ganic oxide paiticles compπse silica gel having a median paiticle size of about 0 05 micion to about 1 micron

The method of claim 20 wherein said porous inorganic oxide particles comprise silica gel having a median paiticle size of about 0 2 micion to about 0 8 micron

The method of claim 20 wheiein said composition is a dentifi ice compi ising humectant - -

The method of claim 20 wheiein said composition fuithei compπses desensitizing additive

The method of claim 28 wheiem the desensitizing additive comprises potassium nitrate or strontium chloride

The method of claim 20 wherein the composition fuithei comprises calcium oxide

The method of claim 20 wherein the composition fuithei compπses calcium phosphate

The method of claim 20 wherein the composition furthei comprises anti-gingivitis agent

The method of claim 20 wheiein the composition f uithei comprises poiyvinylmethyl ethei/maleic acid copolymei

The method of claim 20 wherein the composition fuithei compπses additional inoiganic oxide pai ticles having a median particle size in the l nge of about 8 to about 20 micions

The method of claim 20 wherein the composition fuithei compπses stannous fluoride oi potassium oxalate

The method of claim 20 wherein the composition is in two oi moie parts which are combined pπoi to applying the composition to the dentinal suiface, fuithei wheiein one pait comprises the porous inorganic oxide particles and a second pait compπses calcium oi phosphate salts