ENHANCED TOOTH WHITENING METHOD COMBINING

SUSTAINED RELEASE VARNISH WITH LIGHT ACTIVATION

DESCRIPTION

The following relates to the dental care arts, and related arts and more specifically concerns a method for whitening teeth.

Tooth whitening products that are based on hydrogen peroxide and other bleaching agents, such as carbamide peroxide and sodium percarbonate, include toothpastes, peroxide gel strips, whitening solutions, and mouthwashes. The aim is usually to deliver the whitening agent to the teeth in a sufficient amount to effect a color change in the enamel and dentine of the teeth in an acceptable period of time without causing harm to the user. Some methods rely on using a high concentration (e.g., 25%) hydrogen peroxide gel applications often with light assistance for a short time (e.g., 4x15 minutes). Other methods use a much lower concentration varnish (e.g., 1-6% hydrogen peroxide) for a longer time (e.g., 5-40 hours, either in a single treatment or over several treatments) without high power light assistance. Care has to be taken when using high concentrations of hydrogen peroxide to avoid damage to soft tissue, such as the gums, and thus such methods are often regulated and are best employed by dental professionals. Peroxide gel strips use lower concentrations of hydrogen peroxide or carbamide peroxide , but entail wearing a plastic strip on the teeth to be treated for an extended period, or inserting fresh strips repeatedly over a long period.

A method is disclosed which can overcome some of the problems with existing systems.

In accordance with one aspect of the present disclosure, a method of whitening teeth includes applying a curable whitening varnish composition that includes a matrix material having a bleaching agent dispersed therein, and exposing the cured varnish composition to light energy to enhance the efficacy of the bleaching agent.

The present compositions and methods may take form in various components and arrangements of components, and in various process operations and arrangements of process operations. The drawings are only for the purpose of illustrating preferred embodiments and are not to be construed as limiting the invention.

FIGURE 1 schematically illustrates an exemplary composition applied to the teeth of a user.

FIGURE 2 illustrates an applicator for applying the exemplary composition in accordance with another embodiment disclosed herein.

FIGURE 3 is a flow chart illustrating methods for using the exemplary composition, in accordance with embodiments disclosed herein.

FIGURE 4 schematically illustrates microparticles in accordance with another embodiment disclosed herein.

FIGURE 5 is a flow chart illustrating methods for forming microparticles that may be used to incorporate a bleaching agent into an exemplary composition, in accordance with embodiments disclosed herein.

FIGURE 6 diagrammatically illustrates a device forming a composition in accordance with another embodiment disclosed herein.

With reference to FIGURE 1, a whitening composition 10 in the form of a varnish is shown. The whitening composition includes a matrix material 12 and a tooth bleaching agent 14 dispersed in the matrix material 12. The bleaching agent may be in liquid or powder forms, uniformly distributed or distributed in controlled release microparicles. The matrix material 12 includes a resin component. The resin component can include at least one of a polymerizable monomer and a film-forming polymer, making the present whitening varnish compositions curable. The composition is applied as a layer 16 to teeth 18. The layer 16 may be bounded, on the side away from the teeth 18, by a barrier layer 20 formed from a moisture-resistant material, such as a polymer material which hardens more completely than the underlying matrix material 12.

The matrix material 12 (and the composition 10 containing it) can be adhesive (to the teeth) and/or capable of film forming on the teeth.

The bleaching agent may be present, expressed as the equivalent weight of hydrogen peroxide in the whitening varnish composition 10, at from 0.1 wt. % to 50 wt. %. In one embodiment, the bleaching agent may be present, expressed by weight of hydrogen peroxide, at from 2 wt. % to 25 wt. % of the composition 10, or when formulated for home use, the composition may be from 2 wt. % to 8 wt. % equivalent of hydrogen peroxide, e.g., 6 wt. % equivalent of hydrogen peroxide. The bleaching agent may be homogeneously dispersed in the matrix material.

In addition to the bleaching agent 14, the matrix 12 of the whitening varnish composition 10 may further include particles 30 which serve as viscosity modifiers, such as silica particles, which are dispersed in the resin component of the matrix material 12. Other optional additives which may be present in the composition 10 and/or the barrier layer 20 include other viscosity modifiers, tartar control (anticalculus) agents, abrasives, fluoride ion sources, remineralization agents tooth desensitizers, anticaries agents, antimicrobial agents, antioxidants, anti-plaque agents, anti-inflammatory agents, coloring agents, such as titanium dioxide, flavoring agents, and the like. These additives may each be present in the matrix material 12, the barrier layer 20, or both.

To evaluate candidate compositions for durability and removal, samples of the composition can be applied to teeth, such as bovine teeth or extracted human teeth, tested to see if they cure sufficiently to retain their integrity for a few hours, for example, and can be removed by brushing.

As will be appreciated, FIGURE 1 is intended to be illustrative only and is not intended to be to scale.

FIGURE 2 illustrates an exemplary applicator 34 which can be used to apply the whitening varnish composition 10. The applicator includes a suitably shaped dental tray 36 and a source 38 of light of a curing wavelength. In another embodiment, the composition 10 is applied using a pen type device (not shown) with a brush or sponge tip. Parts of the composition may be stored in separate chambers of the pen to be mixed when the two parts are applied to the teeth. For example, a photoinitiator or curing catalyst may be in one compartment and a monomer in the other. In another example, bleach may be in one compartment in liquid, powder, or microencapsulated form and the varnish in the other . In other embodiments, all components of the composition are kept in a single chamber of the pen. Separate pens may be used for multilayer compositions. The whitening varnish composition 10, when applied on the teeth, may be allowed to cure by itself or in some embodiments at least one of heat, an air jet, and light may be applied to speed up the process. Lip retraction may be used to keep the lips from coming into contact with the composition as it cures. Curing is used herein to describe any process by which the whitening varnish composition forms an intact layer on the teeth which is capable of remaining on the teeth throughout the whitening process. Vibration may be used during curing to improve the smoothness of the layer. Soft tissue in the mouth, such as the gums, may be protected, prior to applying the whitening varnish composition 10.

Method of using the composition

The whitening varnish composition 10 and optional barrier layer 20 may be applied to the teeth 18 of a person, to whiten the teeth.

With reference to FIGURE 3, a method for treating teeth with the exemplary composition is shown. The method begins at SI 00. At SI 02, the whitening varnish composition 10 is provided.

At SI 04 the whitening varnish composition 10 is applied to the teeth of a person or animal to be treated. The composition 10 may be applied by a dental professional, such as a dentist, or by the wearer. For example, the whitening varnish composition 10 may be applied to the teeth using an applicator, such as a pen, brush, piece of foam, or cloth applicator to form a layer. In other embodiments, the composition 10 may be inserted into an applicator, such as into the dental tray 36 of the applicator 34 shown in FIGURE 2, which is positioned adjacent the teeth and then removed, for example, after partial curing of the whitening varnish composition. The whitening varnish composition 10 may be applied to the teeth at a thickness t of for example, from 10-500μιη, such as from 10- ΙΟΟμπι, e.g., about 50μιη. In the exemplary embodiment, the whitening varnish composition is applied to the tooth in a single application to a thickness of 25-100 μιη in thickness, allowing the varnish to be smooth to the touch, when cured.

Optionally, at SI 06, a barrier layer 24 is applied over the layer 16 of composition

10.

At SI 08, the whitening varnish composition 10 may be cured or otherwise hardened to form a film containing the bleaching agent on the teeth. The curing/hardening may be performed with light, moisture, solvent evaporation, or a combination of these. In one embodiment, the matrix material 12 includes a resin component which is moisture- cured, for example, by saliva naturally present on the teeth. In another embodiment, the matrix material includes a solvent which evaporates. In yet another embodiment, the resin component of the matrix material includes a curing agent and is cured by light, such as blue light, form a suitably positioned light source 38. Different compositions for these types of matrix material are discussed below. In one embodiment, the exemplary composition cures rapidly, for example in 10 minutes or less, such as in under three minutes, for example, from thirty seconds to two minutes. For compositions which take minutes or longer to cure, soft tissue in the mouth, such as the lips and/or gums, may be protected with a coating or held away from the teeth, e.g., with a lip retractor.

In one embodiment, the source 38 of light in wavelengths suitable for curing the composition, such as blue light, is positioned adjacent the layer 18 and optional layer 24, if present. The light of the specified wavelength range may be applied by a light source 38 integral with the applicator 34, if used, or by a separate light source. Barrier layer 20 may be cured contemporaneously with the whitening varnish composition 10 or applied subsequently and cured or allowed to cure.

At SI 10, the bleaching agent in the cured whitening varnish composition is activated by the application of light energy. The light energy enhances the chemistry of interaction between bleaching agent and stains on the user's teeth. Incoherent or coherent light may be used for this step of the process, for example, LED or laser light of wavelength 300 to 1100 nm, such as LED or laser light of wavelength 400 to 850 nm, e.g., LED or laser light of wavelength of 540 to 700 nm. In exemplary embodiments, light energy in the visible spectrum of between 400 and 700 nanometers is applied to the varnish-covered teeth. The laser may be chosen to provide a wavelength tailored to the color of the stain molecules so that the energy of the laser is largely absorbed by the stain molecules rather than the tooth tissues.. The application of light energy may be maintained for a treatment period of, for example 3 to 300 minutes, such as 15 to 180 minutes, e.g., for about 30 to 120 minutes. Illumination of the stained teeth may be performed individually tooth by tooth, in small groups of teeth, or simultaneously on all teeth as a whole. The light emerging from the light source may be continuous ("on" the entire procedure), interrupted continuous (primary "on" with short rest interruptions), pulsed ("on" and "off in a predetermined timed sequence and intensity), or a combination of continuous, interrupted continuous and pulse. In exemplary embodiments from about 25 to about 200 milliWatt/cm ² of light is applied continuously to the surface of the teeth. In an exemplary embodiment, bleaching of stained teeth is achieved using an argon ion laser to light activate the bleaching agent. In the visible spectrum, argon produces blue and green light with a wavelength in the range of 450-530 nanometers. In an exemplary embodiment, 465nm blue light is applied at a power density of 25 to 200mW/cm ² . In an exemplary method, after the dental professional (e.g., dentist) applies the varnish composition, the dentist or other dental professional applies strong blue light for a period of time (for example, 1 to 2 hours), chair-side. This may comprise a single treatment, or a multiplicity of shorter applications of varnish and light during the 2 hour chair time. After application of light treatment, the patient may leave the office of the dental professional and the varnish is left on the patient's teeth and continues to whiten after the patient has left the office of the dental professional. This will continue until the varnish is removed at some later time. In exemplary embodiments, the patient may intermittently accelerate further with a portable light emitting mouthpiece at home, whilst the varnish remains intact.

In embodiments, the cured whitening varnish composition is exposed to light in one or more treatments for a total light exposure time in the range of from about 10 minutes to about 120 minutes. In embodiments, light with a wavelength in the range of about 400 nanometers to about 500 nanometers is applied to the cured whitening varnish composition to accelerate the bleaching process. In embodiments, the cured whitening varnish composition is exposed to light four times, and in each of the four times from about 25 to about 200 milliWatt/cm ² of light is applied to the cured whitening varnish composition for a period of about 15 minutes to accelerate the bleaching process, for a total light exposure time of about 60 minutes.

In the exemplary method shown in FIGURE 3, it should be noted that light may be applied for two different purposes; namely, to cure the whitening varnish composition (if the varnish is light-curable) and to accelerate the bleaching process. The light-application parameters for the curing step may be different from the parameters for the bleaching acceleration step. Typically, light curing requires only a short exposure (e.g., 30 seconds to 3 minutes) and bleaching acceleration typically requires somewhat longer exposures (e.g., 10 minutes to 120 minutes).

At SI 12, after sufficient time to effect at least a partial whitening of the teeth, e.g., a change in color of at least 1 ΔΕ, the layer of varnish (and optional barrier layer) is removed. For example, at the end of the treatment period, the composition 10 is removed from the teeth by peeling it away from the teeth and/or by brushing the teeth. In embodiments, the whitening varnish composition remains on the tooth for a period of time ranging from about 30 minutes to about 10 hours after the termination of light treatment. The process may be repeated, for example, once or twice a day, week, or month or less frequently, until a desired color change is effected or to maintain whiteness of the teeth.

ΔΕ is computed according to the CIE76 definition, using the L*,a,*b* values of the teeth (which may be averaged values), before whitening (denoted by the subscript 1) and after whitening (denoted by the subscript 2), according to the formula:

*z = jc¾ - ^L f + o¾ - ^® if + c¾ - ¾f

The method ends at SI 14.

The matrix material 12 is formulated to form a film on the teeth which retains the bleaching agent 14 in close proximity to the surface of the teeth. Over a period of from about 10 minutes to 40 hours, the bleaching agent 14 is released from the matrix material 12 by moisture, activated by the application of light energy, and whitens the teeth by removing stains and optionally whitening the tooth enamel and dentine. In particular, moisture penetrates the matrix material 12, allowing the bleaching agent 14 within the matrix material 12 to migrate toward the tooth 18.

In the exemplary embodiment, due to properties of the matrix material 12 (and optional barrier layer 20), the concentration of bleach in the oral cavity remains fairly low and does not pose a significant risk of damage or irritation to the soft tissue in the mouth. Accordingly, application of the curable whitening varnish composition, curing of the whitening varnish composition and exposing the cured whitening varnish composition to light can be performed without the need for any soft tissue masking. The prolonged contact of the whitening varnish composition 10 with the teeth, however, allows the bleaching agent 14 to be released progressively from the matrix material 12 and, accelerated by the application of light energy to whiten the teeth.

Bleaching Agent

The whitening varnish composition 10 includes a dental bleaching agent. Exemplary bleaching agents are solid at ambient conditions and include carbamide peroxide, which is an adduct of urea and hydrogen peroxide (CH ₄ N ₂ O-H ₂ O ₂ ). This material releases hydrogen peroxide on contact with water. Other example bleaching agents include alkali metal percarbonates, sodium perborate, potassium persulfate, calcium peroxide, zinc peroxide, magnesium peroxide, strontium peroxide, other hydrogen peroxide complexes, sodium chlorite, combinations thereof, and the like. The term "bleaching agent," herein refers to compounds which are themselves bleaches and to compounds which are bleach precursors, such as carbamide peroxide, which react or decompose to form a bleach, such as hydrogen peroxide.

The whitening varnish composition can include the bleaching agent, e.g., carbamide peroxide, at a concentration of at least 5 wt. % or at least 10 wt. %, such as up to about 95 wt. %, or up to about 60 wt. %. 20 wt. % carbamide peroxide, as an example, corresponds to a hydrogen peroxide concentration per particle of about 6 wt. %. Higher concentrations of the bleaching agent may be employed to achieve an overall concentration in the whitening varnish composition 10 of at least 2 wt. % or more, as noted above.

In embodiments, the varnish contains up to 30% hydrogen peroxide when cured. Such compositions formulated with carbamide peroxide may result the release of a level of urea upon contact with water sufficient to impact the properties of the varnish, such as viscosity and cure time. Accordingly, in lieu of carbamide peroxide, such compositions may be formulated using aqueous hydrogen peroxide, such as a solution of 60% hydrogen peroxide in 40% water. Exemplary Varnish Compositions

Suitable whitening varnish composition 10 include self-cured and light-cured compositions.

Illustrative whitening varnish composition 10 may include (the components totaling 100%):

A. 2-95 wt. % (or 5-90 wt. %, or 20-80 wt. %) of bleaching agent; and

B. 98-2 wt. % (or 10-95 wt. %, or 80-20 wt. %) of the matrix material 12, the matrix material consisting of (the matrix material components totaling 100%):

Bl . 1-70 wt. % (or 5-50 wt. %, or 10-20 wt. %) of a resin component, which may comprise at least one of a polymerizable monomer and the reaction product of a polymerizable monomer and a curing agent,

B2. 0-30 wt. % (or 2-20 wt. %, or 5-10 wt. %) of an organic solvent, B3. 0-40 wt. % viscosity modifier, and

B4. 0-50 wt. % (or 1-20 wt. %) other additives (i.e., other than the components A, Bl, B2, and B3), such as one or more of particles, colorants, anti-tartar agents, anti-caries agents, surfactants, antimicrobial agents, antioxidants, anti-plaque agents, and the like.

The matrix material (12) can be substantially free of water (includes less than 5 wt.

% water, or less than 1 wt. % water). In some embodiments, no water is used in forming the composition. Additionally, the components used in forming the composition may be dry, and may be anhydrous, where possible.

A ratio, expressed by weight, of bleaching agent to the matrix material in the composition 10 can range from 1 :50 to 50: 1, such as at least 1 : 10 (or at least 1 :2, or at least

1 : 1, or at least 5: 1, or at least 10: 1, or at least 15: 1).

The resin component Bl can include one or more polymerizable monomers and a curing agent. In some embodiments, the resin component Bl can include a film forming polymer and/or resin. A "monomer," as used herein includes polymerizable monomers, dimers, and oligomers, except as noted. The solvent B2 can be any compatible pharmaceutically-acceptable organic solvent, such as an alcohol, unsaturated hydrocarbon, ketone, or the like, which is liquid and/or volatile at ambient temperatures (20-30°C).

The viscosity modifier may include one or more of particles 30, waxes, gums, and other thickeners.

Illustrative matrix compositions are now described.

1. Self-cure compositions: these include moisture cured varnishes and solvent based varnishes.

a. Moisture Cured Varnishes:

Examples of these include varnishes based on natural resins, such as colophonium resin which cures when in contact with saliva. Varnishes of this type are disclosed for example, in WO2009/124311. Shellac may also be used in such compositions, alone or in combination with another resin. An example moisture-cured matrix material B suited to use in such varnishes 10 may include (totalling 100 %):

Bl . 1-70 wt. % (or 5-50 wt. %, or 10-20 wt. %) of a resin (moisture- cured and/or air-cured),

B2. 1-30 wt. % (or 2-20 wt. %, or 5-10 wt. %) of a solvent,

B3. 0-40 wt. % viscosity modifiers (or 1-20 wt. %, or 5-10 wt. %), such as one or more of:

B3a. particles 30 (e.g., at 1-20 wt. %, or 5-10 wt. %),

B3b. waxes (e.g., 1-20 wt. %, or 5-10 wt. %), and B3b. gums (e.g., 1-20 wt. %, or 5-10 wt.), and

B4. 0-20% (or 1-20%) of other additives.

The composition 10 containing such a matrix material is applied on damp teeth and the mouth closed to allow saliva to cure the resin.

As an example, a matrix composition 12 can be formed from colophonium resin and/or shellac, a solvent, and optionally one or more waxes and/or gums. Example solvents include C1-C20 alcohols and ketones, e.g., ethanol, propanol, cetyl alcohol, stearyl alcohol, and C6-C20 hydrocarbons, such as hexane. Example hydrocarbon waxes include esters of fatty acids and long chain alcohols that are solid or viscous liquids at room temperature. These include naturally occurring waxes such as beeswax, and C40-C100 alkanes and fatty acid esters. Gums, such as mastic (a resin obtained from Pistacia lentiscus Var. Chia) may be included in the matrix material.

One example moisture-curable composition 10 includes a matrix material 12 comprising colophonium resin and an organic solvent (e.g., one or more of ethanol, methanol, n-hexane, and cetostearyl alcohol), and the exemplary microparticles 14.

Another example moisture-curable composition 10 includes a matrix material 12 comprising shellac, colophonium resin, a solvent (such as ethanol), beeswax, and mastic, and the exemplary microparticles 14.

b. Solvent-based varnishes: these are based on solvent evaporation. An exemplary matrix material of this type can include a conventional polyacrylic acid based polymer in combination with a solvent, such as C1-C10 mono-alcohol or polyol, e.g., one or more of methanol, ethanol, n-hexane, and glycerol, and optionally a buffer agent. The polyacrylic acid-based polymer may include functional groups which increase the permeability of the polymer matrix to water, such as ammonium groups, e.g., as their salts.

As an example, the matrix material can be formed from acrylic acid polymers such as Carbomer, optionally a surfactant such as a polysorbate or sorbitan ester (e.g., sobitan monooleate), glycerol, and EDTA as buffering agent. Other components may be present, such as arginine and potassium nitrate.

A composition 10 containing such a resin can be applied on dry teeth and the mouth kept open to allow the resin to cure in 30 seconds to 2 minutes.

An example solvent-based matrix material B may include (totalling 100 %):

Bl . 1-70 wt. % (or 5-50 wt. %, or 10-20 wt. %) of resin,

B2. 1-30 wt. % (or 2-20 wt. %, or 5-10 wt. %) of a solvent, B3. 0-40 wt. % viscosity modifiers, such as particles 30, waxes, and/or gums, and

B4. 0-20% other additives, such as 0.001-5 wt. % of a surfactant and 0.001-5 wt. % of a buffering agent.

In one embodiment, the solvent based varnish may include, in the above amounts: Bl . Copolymer derived from esters of acrylic and methaciylic acid, e.g., available under the tradename Eudragit® from Evonik (e.g., Eudragit® RL PO, a poly(ethylacrylate-co-methyl methacrylate-co-trimethylammonioethyl methaciylate chloride), which is a copolymer of ethyl acrylate, methyl methaciylate and a low content of methaciylic acid ester (ratio of 1 :2:0.2) with quaternary ammonium groups, which are present as their salts. The polymer has the general formula:

B2. Solvent such as n-hexane, ethanol, cetostearyl alcohol

B4. Other additives (optional) to increase efficiency, product delivery, product shelf life and wearer suitability, such as:

Stabilizer such as polyphosphates, benzoic acid, salicyclic acid,

EDTA, sodium perborate

Saliva inhibitor such as sodium fluoride

Flavoring, such as mint or peppermint oil

Emulsifier, such as Tween 20, Span 80

Humectant, such as glycerin, sorbitol, xylitol, PEG

pH control agent, such as sodium bicarbonate, sodium hydroxide, citric acid

This matrix material is combined with a bleaching agent, such as carbamide peroxide, calcium peroxide, sodium perborate, hydrogen peroxide 2. Light-cure varnishes: In the case of light-cured compositions, the resin component Bl may comprise one or more polymerizable monomers Bla, B ib and optionally one or more curing agents Blc, Bid. Example polymerizable monomers may include one or more functional monomers Bla and optionally a crosslinking monomer Bib. The curing agent may include at least one of a photoinitiator B lc and a co-initiator Bid.

An example light-curable matrix material B may include (totalling 100 %):

Bl . 1-70 wt. % (or 5-50 wt. %, or 10-20 wt. %) of resin,

B2. 1-30 wt. % (or 2-20 wt. %, or 5-10 wt. %) of an organic solvent,

B3. 0-40 wt. % viscosity modifying particles 30 and/or waxes, and

B4. 0-20% other additives.

An example light-curable resin component Bl may include (totalling 100 %):

Bla. Functional monomer (e.g., HEMA): 10-50 wt. %

Bib. Crosslinking monomer (e.g., Bis-GMA): 50-90 wt. %

Blc. Initiator (e.g., Camphorquinone): 0.1-2 wt. %

Bid. Co-initiator (e.g., DMAEMA) 0-3 wt. %, e.g., at least 1 wt. %.

Ble. Inhibitor (to reduce self-polymerization in storage) 0-3 wt. %, e.g., at least 0.01 wt. %, such as about 0.1%.

Suitable functional monomers B la include monofunctional and multifunctional acrylates and methacrylates (referred to jointly herein as (meth)acrylates). Suitable (meth)acrylates include those having a viscosity of about 0.1 to about 100 cps at 25°C. Use of multifunctional (meth)acrylates can increase cure speed of the resin composition. Examples of these monomers include hydroxyalkyl methacrylates, such as 2-hydroxyethyl methacrylate (HEMA) and 2-hydroxypropyl methacrylate; ethylene glycol methacrylates, including ethylene glycol methacrylate, diethylene glycol methacrylate, tri(ethylene glycol) dimethacrylate and tetra(ethylene glycol) dimethacrylate; and diol di methacrylates such as butanedimethacrylate, dodecanedimethacrylate, and 1,6-hexanedioldimethacrylate (HDDMA), and mixtures of these.

Suitable crosslinking monomers B ib include bisphenol glycerolate dimethacrylate (Bis-GMA), which is the condensation product of bisphenol A and glycidyl methacrylate; triethylene glycol dimethacrylate (TEDGMA); aliphatic and aromatic polyurethane dimethacrylate (PUDMA); and urethane dimethacrylate (UDMA), and mixtures of these. Other viscous resins having a viscosity of greater than about 1000 centipoise (cps) at 60°C can also be used. The amount of crosslinking monomer can have an influence on mechanical property and viscosity of the resin.

Other examples of suitable (meth)acrylates include higher viscosity

(meth)acrylates, such as aliphatic and aromatic diurethane dimethacrylates (DUDMA), polycarbonate dimethacrylate (PCDMA), a condensation products of two parts of a hydroxyalkylmethacrylate and 1 part of a bis(chloroformate), as disclosed in U.S. Pat. Nos. 5,276,068 and 5,444, 104; and ethoxylated bisphenol A dimethacrylate (EBPDMA), as disclosed in U.S. Pat. No. 6,013,694.

Most methacrylates are moderately hydrophobic. Some form films which are very strong and do not release easily from the teeth. In some embodiments, a first (meth)acrylate Bla, which forms strong bonds with teeth is combined with a second (meth)acrylate Bib, e.g., a dimer, as a crosslinker which forms less strong bonds. As an example, HEMA (hydroxyethyl methacrylate), which is semi-soluble in water, is combined with a less- strong dimer, such as polyethylene glycol (PEG) dimethacrylate (a polymer of ethylene oxide which is terminated at each end by a methacrylate unit). The molecular weight of the PEG can be controlled/chosen to achieve the desired bonding and release properties. This gives cross linking with a weaker backbone and moderate hydrophilicity. As an example, the PEG dimethacrylate can have a number average molecular weight of 100-2000, such as at least 500. Additionally or alternatively, by modifying the stoichiometry, e.g., by overloading the blend with HEMA, the crosslink density can be controlled.

Example photoinitiators Blc include camphoroquinone (CQ), phenylpropanedione (PPD), benzoin esters, benzophenone, acylphosphine oxides, and lucirin. A co-initiator Blc may be used in combination with the photoinitiator, such as a tertiary aliphatic amine, e.g., dimethylaminoethylmethacrylate (DMAEMA).

Suitable co-initiators Bid. include DMAEMA, and aliphatic and aromatic amines (e.g., in the case of CQ as an intiator).

Suitable inhibitors Ble. include butylated hydroxytoluene, butylhydroxytoluene(BHT), monomethyl ether hydroquinone (MEHQ). Exemplary solvents B2 for such resins include C2-C20 alcohols e.g., ethanol, propanol, cetyl alcohol, stearyl alcohol, C3-C20 ketones, such as acetone, and C6-C20 hydrocarbons, such as hexane.

Such formulations may be cured with blue light, or other wavelengths in the visible range. Suitable light absorption/curing is from 400-490nm, such as from 475-480 nm (depending on the actual formulation). As an example, CQ is a photo initiator which absorbs with a peak in the blue wavelength range and produces radicals when excited in the 460-490nm range. Co-initiators, such as DMAEMA, accelerate the light-cure process. When formulated as a composition 10 and applied to dry teeth, the composition may cure in 10 seconds to 1 minute under blue light illumination. PPD uses a shorter wavelength (420-430nm).

As one example, a mixture of acrylic acid, Bis-GMA, CQ, HEMA and optionally DMAEMA is combined with a solvent, such as acetone and/or ethanol, the bleaching agent 14 and optionally silica particles. The composition can cure in 30 seconds under blue light. Such a composition stays intact in excess saliva, and can be completely removed by peeling and brushing.

As another example, a mixture of acrylic acid, itaconic acid, and HEMA is combined with calcium glycerophosphate, Bis-GMA, camphoroquinone, silica beads, and the bleaching agent and applied to the teeth. The composition can cure in 10 to 20 seconds under blue light. Viscosity Modifiers (B3)

The exemplary composition 10 may include at least 1 wt. % (or at least 2 wt. %, or at least 5 wt. %, or at least 10 wt. %, or at least 15 wt. %) of component B3, such as up to 50 wt. %, or up to 20 wt. %.

Component B3 of the composition 10 disclosed herein may include from 0-100 wt. %, e.g., at least 5 wt. % (or at least 20 wt. %, or at least 40 wt. %) of particles 30. The particles may have a Mohs hardness of at least 2 (or at least 3, or at least 5).

Particles 30 may serve as viscosity modifiers and/or abrasives. An abrasive may be useful, for example, as a polishing agent. Suitable particles include silica, for example in the form of silica gel, hydrated silica or precipitated silica, alumina, insoluble phosphates, orthophosphates, polymetaphosphates, and beta calcium pyrophosphate, calcium carbonate, resinous abrasives such as urea-formaldehyde condensation products and mixtures thereof.

Suitable waxes and gums useful as viscosity modifiers include those mentioned elsewhere herein.

Suitable thickeners useful as viscosity modifiers may include starches, anionic polymers, and the like.

Other additives (B4)

The composition 10 may include at least 1 wt. % (or at least 2 wt. %, or at least 5 wt. %, or at least 10 wt. %, or at least 15 wt. %) of component B4, such as up to 50 wt. %, or up to 20 wt. %.

As examples of other additives, the composition 10 may include one or more of the following:

Colorants: The colorant may be selected to provide the film with a white appearance or a tint.

Tartar control (anticalculus) agents: these may include phosphates and polyphosphates (for example pyrophosphates), polyaminopropanesulfonic acid (AMPS), polyolefin sulfonates, polyolefin phosphates, diphosphonates such as azacycloalkane-2,2- diphosphonates (e.g., azacycloheptane-2,2-diphosphonic acid), N-methyl azacyclopentane- 2,3-diphosphonic acid, ethane- l-hydroxy-l,l-diphosphonic acid (EHDP) and ethane-1- amino- 1, 1-diphosphonate, phosphonoalkane carboxylic acids and salts of any of these agents, for example their alkali metal and ammonium salts, and mixtures thereof.

Fluoride ion sources: These may be useful, for example, as an anti-caries agent. Orally acceptable fluoride ion source which can be used include potassium, sodium and ammonium fluorides and monofluorophosphates, stannous fluoride, indium fluoride and mixtures thereof.

Tooth and soft tissue desensitizers: these may include stannous ions, such as halides and carboxylate salts, arginine, potassium citrate, potassium chloride, potassium tartrate, potassium bicarbonate, potassium oxalate, potassium nitrate, strontium salts, and mixtures thereof. Antimicrobial (e.g., antibacterial) agents: these may include orally acceptable antimicrobial agents, such as Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol); 8- hydroxyquinoline and salts thereof, zinc and stannous ion sources such as zinc citrate; copper (II) compounds such as copper (II) chloride, fluoride, sulfate and hydroxide; phthalic acid and salts thereof such as magnesium monopotassium phthalate; sanguinarine; quaternary ammonium compounds, such as alkylpyridinium chlorides (e.g., cetylpyridinium chloride (CPC), combinations of CPC with zinc and/or enzymes, tetradecylpyridinium chloride, and N-tetradecyl-4-ethylpyridinium chloride); bisguanides, such as chlorhexidine digluconate,; halogenated bisphenolic compounds, such as 2,2' methylenebis-(4-chloro-6-bromophenol); benzalkonium chloride; salicylanilide, domiphen bromide; iodine; sulfonamides; bisbiguanides; phenolics; piperidino derivatives such as delmopinol and octapinol; magnolia extract; grapeseed extract; thymol; eugenol; menthol; geraniol; carvacrol; citral; eucalyptol; catechol; 4-allylcatechol; hexyl resorcinol; methyl salicylate; antibiotics such as augmentin, amoxicillin, tetracycline, doxycycline, minocycline, metronidazole, neomycin, kanamycin and clindamycin; and mixtures thereof. Other useful antimicrobials are disclosed in U.S. Pat. No. 5,776,435.

Antioxidants: orally acceptable antioxidants which can be used include butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), vitamin A, carotenoids, vitamin E, flavonoids, polyphenols, ascorbic acid, herbal antioxidants, chlorophyll, melatonin, and mixtures thereof.

Antiplaque (e.g.. plaque disrupting) agent: orally acceptable antiplaque agents can include stannous, copper, magnesium and strontium salts, dimethicone copolyols such as cetyl dimethicone copolyol, papain, glucoamylase, glucose oxidase, urea, calcium lactate, calcium glycerophosphate, strontium polyacrylates, and mixtures thereof.

Anti-caries agents: examples of these include calcium glycerylphosphate and sodium trimetaphosphate.

Anti-inflammatory agents: orally acceptable anti-inflammatory agents can include steroidal agents, such as flucinolone and hydrocortisone, and nonsteroidal agents (NSAIDs) such as ketorolac, flurbiprofen, ibuprofen, naproxen, indomethacin, diclofenac, etodolac, indomethacin, sulindac, tolmetin, ketoprofen, fenoprofen, piroxicam, nabumetone, aspirin, diflunisal, meclofenamate, mefenamic acid, oxyphenbutazone, phenylbutazone, and mixtures thereof.

H? antagonists: antagonists useful herein include cimetidine, etintidine, ranitidine, ICIA-5165, tiotidine, ORF-17578, lupititidine, donetidine, famotidine, roxatidine, pifatidine, lamtidine, BL-6548, BMY-25271, zaltidine, nizatidine, mifentidine, BMY- 52368, SKF-94482, BL-6341A, ICI-162846, ramixotidine, Wy-45727, SR-58042, BMY- 25405, loxtidine, DA-4634, bisfentidine, sufotidine, ebrotidine, HE-30-256, D-16637, FRG-8813, FRG-8701, impromidine, L-643728, HB-408.4, and mixtures thereof.

Nutrients: Suitable nutrients include vitamins, minerals, amino acids, proteins, and mixtures thereof.

Anti-staining agents: such as silicone polymers.

Flavoring agents: any of the flavoring agents commonly used in toothpastes may be used, by way of example.

Forming the Composition

Exemplary methods of forming the whitening varnish composition 10 include weighing and dissolving the components of the composition in ethanol with stirring. In an exemplary method, the bleaching agent is added first to the solvent, then the resin material is added with stirring.

The exemplary whitening varnish composition 10 may be formulated for home use or for use by a dental professional. They may be employed in professional treatments where high concentrations of bleaching agent activated in a short period of time. Since the hydrogen peroxide migration is local toward the teeth, the composition containing the exemplary bleaching agent may be used without soft tissue isolation. Alternatively, the compositions 10 may be used for home treatments. For example, the whitening composition may be applied, and the hydrogen peroxide released slowly and locally over an extended period.

While the exemplary compositions are particularly suited to tooth whitening, it is to be appreciated that they may find use in other bleaching applications.

In one embodiment, the bleaching agent is microencapsulated to form microparticles 114 as illustrated in FIGURE 5 prior to being mixed with the resin. As seen in Figure 5, each microparticle 114 includes a core 22, formed of the bleaching agent, which is encapsulated in a shell 24 formed of a carrier material. The carrier material can be formed of any suitable material, which is different, at least in some respects, from that of the core, to space the bleaching agent from the matrix material 12 and/or to modify the rate of release of bleaching agent from the composition, and can be a solid at ambient temperature.

The exemplary carrier material forming the shell 24 may include a hydrophobic material 26 and optionally a release rate modifier 28 in contact with, e.g., dispersed in, the hydrophobic material 26. In other embodiments the hydrophobic material 26 and release rate modifier 28 may form two distinct layers, with the hydrophobic material forming the outermost layer. The microencapsulation may serve to control release of the bleaching agent from the core and/or to separate the bleaching agent from other chemicals in the varnish with which it might react. In some embodiments, the matrix material can provide for slow release of the beaching agents and the microencapsulation simply the separation, in which case, the shell 24 may provide a quick release from the microparticles. In other embodiments, the shell provides for slow release of the beaching agents.

The exemplary microparticles 114 are generally spherical in shape. They can be dry, solid particles of up to 200 micrometers (μπι) in diameter, on average, or up to 100 μπι in diameter. By "solid" it is meant that the particles are solid at ambient temperatures, e.g., solid at a temperature of up to 30°C, at least. By "diameter," it is meant the average dimension, to the extent that the particles are non- spherical. For example, the microparticles 114 can be at least 1 or at least 10 μπι in diameter, on average, and in one embodiment, at least 20 μπι in diameter on average. In some embodiments, the microparticles 114 are up to 50 μπι in diameter, on average. The core 22 may occupy from 1 to 99% of the volume of the microparticle, such as from 10-90%, on average. The shell 24 may be at least 20 nm in thickness, on average, such as at least 0.1 μπι, or at least 1 μπι in thickness, and in some embodiments, up to 40 μπι in thickness, on average. The core 22 may be at least 0.1 μπι in diameter, on average, such as at least 1 μπι in diameter, and in some embodiments, at least 10 μπι, or at least 20 μπι, and can be up to about 100 μπι, in average diameter. In some embodiments, the core may be up to 10 μηι, or up to 20 μηι, or up to 50 μηι in average diameter. In one embodiment, the microparticles 114 have a core which is up to 15 μιη in average diameter and the microparticles 114 are between 20 and 100 μηι in average diameter. A ratio of a weight of the shell 24 to a weight of the core 22 can be for example, from 0.1 :99.9 to 99.9:0.1, or 1 :99 to 99: 1, or 10:90 to 90: 10, or 50:50 to 70:30, such as 60:40.

The core 22 may be partly or entirely formed from the dental bleaching agent. For example, at least 10%, or at least 20%, or at least 50%, or at least 80%, by weight of the core and up to 100% by weight is bleaching agent.

The microparticles 114 can include the bleaching agent, e.g., carbamide peroxide, at a concentration of at least 5 wt. % or at least 10 wt. %, such as up to about 95 wt. %, or up to about 60 wt. %. 20 wt. % carbamide peroxide, as an example, corresponds to a hydrogen peroxide concentration per particle of about 6 wt. %. This relatively low level may be suited to home use, particularly when the microparticles at relatively high concentrations in the composition (such as at least 20 wt. % or at least 50 wt. % of the composition). However, higher concentrations of the bleaching agent in the particles may be employed to achieve an overall concentration in the composition 10 of at least 2 wt. % or more, as noted above.

Additives, such as any of those listed above as components of the matrix material, may alternatively or additionally be incorporated in the microparticles 114.

In some embodiments, the shell 24 provides a moisture-resistant barrier which releases the bleaching agent slowly, on contact of the microparticle 114 with water, such as with saliva on the teeth or moisture within the teeth. This provides a controlled release of the bleaching agent. In some embodiments, controlled release of the bleaching agent is provided solely or partly by the matrix material 12 and the shell 24 serves to separate the bleaching agent from components in the matrix material 12 with which it may react, such as water and or organic solvents, e.g., alcohols.

In some embodiments, the hydrophobic material 26 of the shell 24 is a water- insoluble and/or hydrophobic material, such as a waxy solid, i.e., is solid at ambient temperature (25°C) and may be a solid at relatively higher temperatures. Exemplary waxes suitable to use as the hydrophobic material include hydrocarbon waxes, such as paraffin wax and the like, which are substantially or entirely free of unsaturation. Exemplary paraffin waxes are higher alkanes and mixtures of higher alkanes of the general formula C„H¾+2, where typically, 20 < n < 50, and thus have no unsaturation. They are solid at ambient temperatures and melt-processable. The melting point of the waxy solid may be within the range of from 30°C to 100°C. To avoid decomposition of the bleaching agent in the core, the waxy solid may have a melting point of below 80°C, and in one embodiment, below 65°C. Paraffin waxes with a melting point of 40°C-60°C may be used, by way of example. Paraffin wax with a melting point of 53-57°C can be obtained from Sigma- Aldrich. Other paraffin waxes are available with melting points of 45°C, 50-52°C, 53-57°C, and 60°C. The melting point of waxes is determined according to ASTM D87 - 09, "Standard Test Method for Melting Point of Petroleum Wax (Cooling Curve)."

The hydrophobicity of the hydrophobic material 26 can be expressed in terms of its contact angle to water. In one embodiment, the water contact angle is at least 75°, such as at least 85°, and in some embodiments, at least 100°, such as up to 120°. The water contact angle can be determined using a contact angle goniometer, for example. The contact angle can be measured on a flat sheet of wax prepared by spraying the molten wax onto a smooth surface, such as a plastic Petri dish to form a wax layer with thickness of approximately 5 mm. After solidification, the rigid, flat wax layer can be removed from the Petri dish and cut into sheets suitable for contact angle analysis. The contact angle of water in air on the surface of such a sheet can be measured using a goniometer, such as an EasyDrop™ (Kruss, Germany). 7[iL of double distilled water in a micro-syringe is dropped on the surface of the sheet placed on a moveable sample stage. The drop is illuminated from one side and the camera on the opposite side records and images the drop. This image is then analyzed by DSA software to calculate the contact angle.

By way of example, two different molecular weights of paraffin wax with melting point of 50-52°C and 53-57°C (Sigma Aldrich, UK) were tested and the measured contact angle was 110.3° ±0.5 and 111.0° ±1, respectively.

The release rate modifier 28 controls the rate of release of the bleaching agent from the core of the microparticles 1 14. Exemplary release rate modifiers 28 include hydrophilic organic polymers which are capable of hydrogen bonding and that are solid at ambient temperatures (25°C), hydrophilic and/or water soluble powders, and combinations thereof. The release rate modifier 28 is more hydrophilic than the hydrophobic material 26. The release rate modifier may be dispersed in the hydrophobic material. In the case of organic polymers, the release rate modifier 28 may be a material which is insoluble or substantially insoluble in the hydrophobic material 26 such that it forms discrete regions where it is of high concentration in the hydrophobic material (or forms a separate layer). The regions may be spaced from each other by the hydrophobic material 26. In the case of hydrophilic and/or water soluble powders as the release rate modifier, the powder may be dispersed throughout the hydrophobic material, or in one embodiment, more highly concentrated near an outer surface thereof. The release rate modifier(s) may be present in the particles 12 at a total concentration of from 0.001 wt. % to 40 wt. %.

In the case of hydrophilic and/or water soluble powders as release agents, these may be present in the microparticles 114 in a total concentration of from 0.001 wt. % to 30 wt. %, such as 0.1- 20 wt. %, or 1.0 to 10 wt. %. Examples of hydrophilic powders include anhydrous inorganic particles, such as silicon dioxide, e.g., hydrophilic silica and silica nanopowders. Exemplary water-soluble powders include water-soluble acids and salts thereof, such as anhydrous phosphate salts, e.g., sodium polyphosphate, sodium tripolyphosphate, sodium pyrophosphate; anhydrous citric acid and salts thereof, such as alkali metals salts, e.g., sodium citrate; anhydrous sodium sulfate, anhydrous magnesium salts, such as magnesium sulfate and magnesium chloride. Combinations of such release agents may be employed. The hydrophilic and/or water soluble powders remain solid during formation of the shell. The hydrophilic and/or water soluble powders, such as silica, may have an average particle size of, for example, 1-100 nanometers (nm), e.g., 5-20 nm, and a surface area of, for example 50-400 m ² /g. Hydrophilic fumed silica, for example, may be obtained under the tradename AEROSIL™ from Evonik Industries with a specific surface area (measured by the BET method) in the range of 90-300 m ² /g. As an example, AEROSIL™ 200 has a specific surface area of 200 m ² /g.

When hydrophilic organic polymers are used as release rate modifiers 28, these may be present in the microparticles 114 at a total concentration of from 0.5 wt. % to 40 wt. %., e.g., 1-35 wt. %, or 10-30 wt. %. The hydrophilic organic polymers may be liquefied during formation of the shell. In one embodiment, the hydrophilic polymer has a melting point of at least 30°C or at least 40°C, such as up to 80°C. The hydrophilic polymer can have a weight average molecular weight of at least 300. Examples of suitable hydrophilic organic polymers include polyalkylene glycols, such as polyethylene glycol and polypropylene glycol, and esters thereof, polyamide compounds (e.g., polyvinylpyrrolidone), poly(vinyl acetate), poly(vinyl alcohol), poly(acrylic acid), polyacrylamide, polyoxylglycerides, such as lauroyl, oleoyl, and stearoyl polyoxylglycerides, which are mixtures of monoesters, diesters, and triesters of glycerol and monoesters and diesters of polyethylene glycols (e.g., lauroyl macrogolglycerides, such as GELUCIRE™ 44/14, available from Gattefosse, which has a melting point of 44°C and an HLB of 14), and ethylene oxide derivatives thereof, poloxamers, which are triblock copolymers having a central hydrophobic block of poly(propylene oxide) and two side blocks of poly(ethylene oxide) (e.g., poloxamer 188, which has a melting point 52°C), and derivatives thereof, and mixtures thereof.

Exemplary polyethylene glycols (PEG) suitable for the release rate modifier may have a weight average molecular weight of from 300 daltons to 50,000 daltons, such as about 600-35000, or 1000 to 5,000 daltons. Such materials are commercially available as PEG 1000 (melting point 37-40°C), PEG 1500 (melting point 44-48°C), PEG 2000 (melting point 49-52°C), and the like. A combination of polyethylene glycols having different molecular weights may be employed to tailor the release rate. For example a mixture may be formed by combining, e.g., in a ratio of from 1 : 10 to 10: 1, a polyethylene glycol having a molecular weight of about 500-1200 (on average), such as PEG 1000, with a polyethylene glycol having a molecular weight of at least 1500 or at least 1800 (on average), such as PEG 1500 or PEG 2000. In one embodiment, a combination of PEGs with average molecular weight ranging from 300 daltons to 50,000 daltons may be mixed on appropriate amounts to provide a mixture which is liquid at a temperature of 35-70°C, such as 45-60°C. For example, PEG with an average molecular weight of 20,000 and PEG 1500 have melting points of 60-65°C and 44-48°C, respectively, and a mixture of PEG 1500 and PEG 20,000 may be liquid at about 55°C, depending on the ratio. In the case of hydrophilic organic polymers, such as PEG, the discrete regions in which the polymer is localized may have an average size of, for example, at least 0.1 or at least 0.5 nm, and can be up to 100 nm, or up to 20 nm, e.g., 0.5-5 nm. For example, the hydrodynamic radius of glycerol is 0.3 nm and that of PEG 1000, PEG 2000 and PEG 4000 is approximately 0.9, 1.4 and 1.9 nm, respectively.

A ratio of hydrophobic material 26 to the release rate modifier 28 in the microparticles 114 may be from 1 :99 to 99: 1, expressed by weight, such as from 2:98 to 98:2, or from 10:90 to 90: 10, or from 15:85 to 85: 15. The ratio can be at least 30:70, or at least 40:60, or at least 60:40. For example, in the case of polymers, such as PEG, the ratio of hydrophobic material to release rate modifier may be about 60:40 or about 50:50. For hydrophilic and/or water soluble powders, the ratio of hydrophobic material to the release rate modifier may be higher, such as at least 85: 15, or at least 90: 10.

The microparticles 114 generally have a low water content, such as less than 5 wt. %, or less than 1 wt. %, or less than 0.2 wt. % of the microparticles 114 is made up of water (free and bound).

In some embodiments, the release rate modifier 28 increases the rate of release of the bleaching agent, as compared with the hydrophobic material 26 alone. For example, the amount of bleaching agent released from the microparticles 114 with the exemplary release rate modifier 28 (e.g., expressed as weight of hydrogen peroxide), may be at least 10% greater or at least 50% greater, over an initial period of two hours, than for the equivalent microparticles formed without the release rate modifier 28, when exposed to the same aqueous conditions (e.g., a buffered release medium, at a temperature of 30-40°C, e.g., as discussed in the Example below). By "equivalent microparticles," it is meant the microparticles are identically formed except that no release rate modifier is employed.

In some embodiments, the release rate modifier 28 may provide the exemplary microparticles 14 with a more uniform rate of release of hydrogen peroxide than equivalent microparticles formed without the release rate modifier 28, when exposed to the same aqueous conditions (e.g., buffered release medium at a temperature of 30-40°C). For example, the initial release rate (expressed as wt. of hydrogen peroxide/hr), over about two hours, may be, on average, less than that of equivalent microparticles without the release rate modifier and may be on average, higher than that of equivalent microparticles in the subsequent two hour period.

In some embodiments, the exemplary microparticles 14 formed with the release rate modifier 28 release at least 10%, or at least 20%, or at least 30% by weight of the total amount of bleaching agent (expressed in terms of hydrogen peroxide) that they contain over a period of 12 hours after contact of the composition 10 with the teeth or aqueous medium at 30°-40°C. In some embodiments, the exemplary microparticles formed with the release rate modifier 28 release less than 40%, or at less than 30%, or less than 25% by weight of the bleaching agent (expressed in terms of hydrogen peroxide), over a period of 4 hours after contact with the teeth or with an aqueous medium at 30°-40°C.

As will be appreciated from the foregoing, the amount and type of release rate modifier can be selected to tailor the release rate according to the desired application. For example, if the composition 10 containing the microparticles 114 is to remain in contact with the teeth for a period of several hours, a slower release rate may be more desirable than when the composition is to be removed more quickly.

In one embodiment, the shell 24 may further include an emulsifier, dispersed in the hydrophobic material. Exemplary nonionic surfactants suitable as emulsifiers include fatty acids, polyol fatty acid esters, such as poly glycerol esters, fatty alcohol polyglycol ethers, alkylphenol polyglycol ethers, fatty acid polyglycol esters, fatty acid amide polyglycol ethers, fatty amine polyglycol ethers, alkoxylated triglycerides, mixed ethers and mixed formals, optionally partly oxidized alk(en)yl oligoglycosides or glucuronic acid derivatives, fatty acid-N-alkyl glucamides, protein hydrolyzates (particularly wheat-based vegetable products), sugar esters, sorbitan esters, polysorbates, amine oxides and combinations thereof. As examples of suitable emulsifiers, nonionic surfactants with a low hydrophile-lipophile balance (HLB) may be used. The HLB may be from 2-5. Surfactants that are able to form micelles are able to improve the stability of hydrogen peroxide. Examples of these emulsifiers include C12-C24 fatty acids, such as lauric acid (C12), myristic acid (C14), palmitic acid (C16), stearic acid (C18), oleic acid (C18), linoleic acid (CI 8), and mixtures thereof. Such fatty acid emulsifiers can be obtained from Sigma- Aldrich under the tradename SPAN™, such as SPAN™ 60, which has an HLB of 4.7, SPAN™ 65, with an HLB of 2.1, SPAN™ 80, with an HLB of 4.3. Exemplary polyglycero] esters include polyglycerol polyricinoleate (PGPR), which has an HLB of 3, and is available from Evronik Industries, Essen Germany, or Danisco. A blend of surfactants having a high HLB and low HLB value may be used.

The emulsifier may be present in the microparticles at a concentration of at least

0.001 wt. %, such as at least 0.1 wt. %, or at least 1 wt. %, and can be present at up to 5 wt. % or up to 10 wt. %, e.g., about 2 wt. %.

Release rate modifiers and emulsifiers may be suitably selected such that they do not adversely affect the stability of the bleaching agent, e.g., of hydrogen peroxide.

Mechanisms by which the release rate is controlled by the release rate modifier are proposed by way of example. In one embodiment, the release rate modifier 28 dissolves in water, leaving pores 40 in the shell 24 where the release rate modifier was previously located. In other embodiments, the release rate modifier attracts and/or absorbs water, increasing in volume and causing a localized disruption in the integrity of the shell.

For example, in the case of a wax/PEG mixture as the encapsulation medium, the wax is hydrophobic, repelling water, while the solid PEG is hydrophilic, attracting water. The release rate can be engineered by varying the ratio of these components. When water is present, it is attracted to hydrophilic regions on the surface of the microsphere (FIG. 1) that are defined by the regions of PEG release rate modifier, or through small cracks in the hydrophobic layer to an underlying hydrophilic layer. The PEG region/layer becomes the site of a pore as water swells the PEG. When a pore penetrates to the carbamide peroxide core 22, the core releases hydrogen peroxide when it gets wet.

The emulsifier present may also affect the release rate.

In some embodiments, the core 22 and/or shell 24 may include additives, such as colorants, preservatives, abrasive materials, emulsifiers, and the like.

A method for optimizing a release rate of the bleaching agent from the particles may include formulating sets of microparticles, each set having a different ratio of hydrophobic material to release rate modifier and testing the sets of microparticles to determine the release rates or amount of bleaching agent released in a selected time period. The method can further include selecting an optimal ratio of hydrophobic material to release rate modifier, based on the results of the tests, for example, to provide a desired release rate of the bleaching agent. Similar tests may be performed with combinations of release rate modifiers and/or emulsifiers, such as different combinations of PEG molecular weight, and selecting a combination of release rate modifiers to identify an optimal combination of release rate modifiers for optimizing a release rate of the bleaching agent. Various combinations of these tests are also contemplated.

Exemplary methods of forming the composition 10 containing microparticles 114 are illustrated in Figure 5. The method begins at S120. At S122, the hydrophobic material is melted. At S124, separately or with S122, the release agent may be melted (e.g., in the case of PEG). At S126 the hydrophobic material and release agent may be combined, if not already combined in S122. A molten mixture of the hydrophobic material and release rate modifier may be formed, for example, by heating the hydrophobic material, and optionally the release rate modifier and emulsifier, to a sufficient temperature to melt at least the hydrophobic material. The components may be stirred to disperse the release rate modifier throughout the hydrophobic material to form a shell material. At S128, the bleaching agent may be coated with the shell material. The bleaching agent is incorporated into the molten mixture, for example, by combining solid particles of bleaching agent with the molten mixture. The molten mixture is separated into solid microparticles (S130), for example, by spraying the mixture into a coolant, such as carbon dioxide, or dissolving the mixture in liquefied carbon dioxide and quickly releasing the pressure, or spraying the mixture onto a cooled surface. At SI 32, the solid microparticles are combined with matrix material 12. The method ends at SI 34.

In another embodiment, suited to forming the composition 10, the method proceeds from S124 to S136, where the bleaching agent, e.g., in particulate form, is coated with a layer of the molten release agent, and, thereafter, at S138, by a layer of the hydrophobic material. The method then proceeds to SI 30. As will be appreciated, steps SI 36 and S138 may be reversed and/or repeated one or more times.

The microparticles 114 can be formed by a variety of methods including spray cooling, precipitation, and the like. Spray cooling/chilling methods can be used where the molten hydrophobic material containing the core material is sprayed into a cold chamber or onto a cooled surface and allowed to solidify. For example, small particles of carbamide peroxide, or other bleaching agent, are combined with a molten mixture of wax and release rate modifier, e.g., PEG. The mixture is sprayed through a nozzle into a fluid at a sufficiently low temperature to solidify the mixture as microparticles. For example, carbon dioxide at low temperature may be used as the cooling fluid.

FIGURE 6 schematically illustrates an exemplary apparatus 50 for forming the microparticles 114. A first reservoir 52 holds the bleaching agent, e.g., a solution of the bleaching agent in a suitable solvent, such as carbamide peroxide dissolved in glycerol, or carbamide peroxide powder dispersed in a liquid. The contents of the first reservoir 52 may be agitated with an agitator 54, such as a vibrator, stirrer, rotation device, or the like. A second reservoir 56 holds the carrier material, e.g., a mixture of molten wax and PEG. A nozzle assembly 58 includes an inner nozzle tube 60, connected with the first reservoir 52, and a concentric outer tube 62, connected with the second reservoir 56. A jet of bleach agent (e.g., pressurized by a pump or the like), exits the first nozzle tube 60 into a concentric annular jet of molten carrier material from the second nozzle tube. The nozzle assembly 58 terminates in a chilled vessel 64, which is optionally fed with a coolant, such as carbon dioxide at low temperature and optionally under pressure, through a feed tube 66. The molten carrier solidifies upon exiting the annular jet. The release rate modifier may be present in the inner and/or the outer jet. In another embodiment, the particles 14 may be formed on contact with a chilled surface.

In other embodiments, C0 ₂ at low temperature and optionally under pressure is used to encapsulate the bleaching agent in PEG or other polymer as first coat, and then a thin layer of wax is applied to avoid rapid dissolution.

Other methods for forming encapsulated particles 114, which may be used herein are disclosed, for example, in U.S. Patent No. 4,919,841, to Kamel, et al. (deposition and annealing of wax coated particles), U.S. Pat. Nos. 4,078,099, 4, 136,052 and 4,327, 151, all to Mazzola (spray methods), EP 0 132 184 to Scotte (spraying encapsulant onto bleach in a mixer), U.S. Pat. Nos. 3,015, 128, 3,310,612 and 3,389, 194 to Somerville, et al. (concentric tube with rotary head), U.S. Pat. No. 3,943,063 to Morishita, et al. (core dispersed in film forming polymer solution), U.S. Pat. No. 3,856,699 to Miyano, et al. (crushed, wax- covered core particles are heated in an aqueous medium), U.S. Pat. No. 3,847,830 to Williams, et al. (peroxygen compounds are held in a fluidized bed and enveloping agent is molten hot prior to spraying onto the peroxygen particles), and EP 0 337 523 (spray drying methods). Other encapsulation techniques are disclosed in MICROENCAPSULATION: Methods and Industrial Applications, Edited by Benita and Simon (Marcel Dekker, Inc., 1996).

The following examples, which are not intended to limit the scope of the invention, demonstrate how the release rate can be tailored using different release rate modifiers and provide illustrative matrix compositions.

EXAMPLES

EXAMPLEl : Production of a self-curing whitening varnish composition

Reagents

As a whitening agent, carbamide peroxide was obtained from Sigma (15-17% active oxygen basis, 04078, Fluka). The particle size distribution of the carbamide peroxide in this material is relatively broad with particle size ranging from 200 to 2000 μπι and the majority of crystals being around 800 μπι.

As a resin, EUDRAGIT® RS PO was obtained from Evonik Industries. EUDRAGIT® RS PO is a copolymer of ethyl acrylate, methyl methaciylate and a low content of methacrylic acid ester with quaternary ammonium groups. The ammonium groups are present as salts and make the polymers permeable.

Ethanol was used as a solvent.

To make the composition, ethanol was added to a vessel and the bleaching agent was added with stirring. Once the carbamide peroxide was dissolved in the ethanol, the resin was added with continued stirring. The final composition contained:

8 % carbamide peroxide

37.5% EUDRAGIT ^® RS PO

53.5% ethanol

This three component composition gives 6% hydrogen peroxide by weight in the cured varnish on the tooth. Another self-curing whitening varnish composition was prepared which contained: 16.6 % carbamide peroxide

28.9% EUDRAGIT ^® RS PO

53.5% ethanol

This three component composition gives 12% hydrogen peroxide by weight in the cured varnish on the tooth.

Testing on stained bovine teeth and extracted human teeth

The staining procedure for the bovine teeth was as follows: A staining solution was prepared from 3 g of fine ground leaf tea, 3 g of fine ground coffee, and 300ml of boiling ddH ₂ 0. This was allowed to infuse for lOmin with stirring. The solution was filtered and cooled to 37°C. Open sides of the tooth samples are sealed with clear nail varnish. The teeth are then etched using sequential immersion in 0.2M HC1, saturated Na ₂ C0 ₃ , 1% phytic acid (30 sec each) and finally rinsed with dd H ₂ 0.

Bovine substrates: 10mm x 10mm bovine incisor fragments were mounted in clear resin, 600 grit finished surface, unsealed. Substrates were stored at 100% relative humidity at 4°C in dd H ₂ 0 or in PBS solution prior to staining and were not allowed to fully dry out.

Bovine tooth samples to be stained were kept in 200 ml of the staining solution for 4 days then rinsed with Millipore water and stored in PBS solution.

The whitening varnish composition, as described above, is applied to each tooth to a thickness Of

20-50um. The composition self-cured in under 1 minute. Initial L*, a*, b* values were measured.

Extracted human substrates: 10mm x 10mm extracted human incisor fragments were mounted in clear resin, 600 grit finished surface, unsealed. Substrates were stored at

100%) relative humidity at 4°C in dd H ₂ 0 or in PBS solution and were not allowed to fully dry out. The whitening varnish composition, as described above, is applied to each tooth to a thickness of 20-50um. The composition self-cured in under 1 minute. Initial L*, a*, b* values were measured.

Half of the varnished coated teeth were then exposed to 465nm light at a power density of 190 mW/cm2 for four treatments of fifteen minutes each. At the end of the sixty minute light treatment, final L*, a*, b* values were measured. The other half of the teeth were not exposed to light. After the cured varnish dwelled on the teeth not receiving light treatment for sixty minutes, final L*, a*, b* values were measured. For comparison, both bovine and human teeth were similarly treated with a 6% hydrogen peroxide gel and a 25% hydrogen peroxide gel (the 25% gel is commercially available under the tradename ZOOM from Philips Oral Healthcare), the 12% varnish described above, and 25% Zoom. The results are shown in Table A.

TABLE A

As can be seen from the data in Table A, the use of light resulted in significantly improved whitening compared to the samples not exposed to light, with ΔΕ values of 6 to 8 being achievable in one hour of treatment.

Each of the documents referred to above is incorporated herein by reference.

Except in the Examples, or where otherwise explicitly indicated, all numerical quantities in this description specifying amounts of materials, reaction conditions, molecular weights, number of carbon atoms, and the like, are to be understood as modified by the word "about." Unless otherwise indicated, each chemical or composition referred to herein should be interpreted as being a commercial grade material which may contain the isomers, by-products, derivatives, and other such materials which are normally understood to be present in the commercial grade. It is to be understood that the upper and lower amount, range, and ratio limits set forth herein may be independently combined. Similarly, the ranges and amounts for each element of the invention may be used together with ranges or amounts for any of the other elements. As used herein any member of a genus (or list) may be excluded from the claims. The invention has been described with reference to the preferred embodiments. Obviously, modifications and alterations will occur to others upon reading and understanding the preceding detailed description. It is intended that the invention be construed as including all such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.