AU2017203653A1 - Photoactivatable oxygen-evolving compositions and methods for teeth whitening - Google Patents

Abstract

Disclosed herein are compositions that can rapidly evolve oxygen and/or activated oxygen generally including an oxidizing agent (e.g., a peroxide) and an activating agent 5 that has an emission wavelength between about 400 nm and about 570 nm (e.g., Eosin B, Eosin Y, or Erythrosine B). Methods of employing these compositions to whiten teeth, and methods of making these compositions and kits that include some or part of the composition ingredients, are also described.

Description

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m in mo (N O (N PHOTOACTIVATABLE OXYGEN-EVOLVING COMPOSITIONS AND METHODS FOR TEETH WHITENING The present application is a divisional application of Australian Application 5 No. 2015203605 , which is incorporated in its entirety herein by reference. CROSS-REFERENCE TO RELATED APPLICATION This application claims priority to and is a continuation of U.S. Patent 10 Application Serial No. 12/771,105, filed April 30, 2010, which is a continuation-in-part of U.S. Patent Application Serial No. 11/598,206, filed on November 9, 2006, the contents of which are hereby incorporated by reference. 15 20 25 30 35 FIELD OF THE INVENTION The present invention relates generally to compositions that evolve oxygen and/or activated oxygen, which are useful in applications such as teeth whitening. More specifically, the invention relates to teeth whitening compositions and kits that can be employed to provide a desired whitening effect (e.g., at least two shades of whitening) in less than about 5 minutes of total exposure to actinic light without significant posttreatment sensitivity. BACKGROUND OF THE INVENTION Peroxide and peroxyacid compounds, such as hydrogen peroxide and carbamide peroxide, have been disclosed as useful in teeth whitening compositions. Application of UV or visible light from, e.g.. Argon lasers, has been employed to accelerate whitening after application of peroxide compositions to the teeth. Additionally, whitening compositions have been described that include compounds capable of absorbing light and converting it to heat or chemical energy, such as the metal-ligand complexes and metal chelate precursors described in US Patent No. 6,343,933 to Montgomery et al. Red dyes have also been employed to absorb visible or UV energy and produce heat in a bleaching composition as described, e.g., in US Patent No. 6,485,709 to Banerjee et al. This patent also describes attempts to further enhance such compositions by adding metal ions, or an organo-metallic enzyme (e.g., catalase), or by using high pH (e.g., above 7) to destabilize or activate the decomposition of hydrogen peroxide. Teeth - 1 -

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m irt so mo (N r-o (N whitening compositions have also been described that include violet or blue-violet dyes to counter-stain yellow teeth in US Patent No. 6,030,222 to Tarver. Rhodamine B dye has been - - la -

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cn m o (N r- o (N r- emplo\ ed in a teeth \\ hitening composition as described in WO 02/22097 to Verhe\ en et at.

Tooth sensitivit}· follo\\ing treatment, and the time required for teeth A\liitening compositions (t\ picalh requiring about an hour of time or multiple applications or both), 5 Ιιο\Λ e\ er, remains a significant dra\> back.

SUMMARY OF THE INVENTION

The present in^ention pro\ides no\el compositions and methods that that e\ohe 10 oxygen and/or acti\ated oxygen and are capable of. for example, whitening teeth in a surprisingh short amount of time (e.g., less than 1 minute to about 10 minutes) and w ith minimal or no sensiti\ it> post-treatment. The in\ ention is based, in part, on the discover\' that the use of the d\ es described herein dramaticalh accelerates the w hitening process.

Without wishing to be bound to an> particular theon. it is believed tliat inclusion 15 of these d> es significanth enhances the compositions of the invention at least because it is believed that dentin transmits green liglit and absorbs blue light. Accordingh, the d> es of the present in\ ention enhance whitening not onl\ at the surface of the tooth, but also ma> be transmitting light into the tootli to enhance the alteration of color agents b>' radicals that ha\ e penetrated into the tooth surface, 20 Another advantage of the present iiwention is that the compositions can be effective when applied only for a short period of time (e.g., 1 minute in some embodiments). Accordinglj·, sensitivity due to, e.g, percolation of Iw drogen peroxide to the pulp tissue (e.g, pulpal inflammation), may be minimized or eliminated. Another advantage of the present in\ ention is that the compositions do not require compounds that 25 generate heat, and therefore, discomfort associated with compositions that generate heat ma>· be minimized or eliminated. Yet another adr antage is that d> es can be used (e.g, Eosin) that are less toxic than d> es such as Rliodamine B.

In one aspect, tlie present in\ention features a tooth whitening composition which includes an oxidizing agent and an activating agent having an emission wavelength 30 between about 40() nm and about 570 nm. ο (Ν σ3 cn cn Ό cn Ο (Ν r- Ο (Ν Γ--

In one embodiment, the acti\ ating agent is capable of emitting green light, blue light or blue-green light, aitd/or absorbs green light, blue light or blue-green light. In another embodiment, the activating agent comprises Eosin (eg., eosin Y, eosin B), Er\ throsine, or both, 5 In another embodiment, tlte composition further includes a stabilizing agent.

In one embodiment, the stabilizing agent is sodium acetate.

In one embodiment, the composition further includes a thickening agent.

In one embodiment, tlte thickening agent is silicon dioxide and/or fumed silica having a particle size less than one micron. 10 In one embodiment, the composition further includes a h> drophilic gelling agent.

In another embodiment, the composition further includes an accelerator agent. In some embodiments, the accelerator agent includes sodium perborate.

In one embodiment, the pH of the composition is betw een about 8 and about 10. 15 The inr ention also features a method for tooth w hitening including apph ing the tooth whitening composition of the present in\ ention to at least one tooth, and exposing the tooth ^vhitening composition to aclinic light such that the tooth is whitened at least about one shade. In one embodiment, the tootli is whitened at least about two shades in less than about 10 minutes or in less than about 5 minutes. 20 In one embodiment, post-treatment sensiti\ ity is insignificant or eliminated.

In one embodiment, the tooth is exposed to the tooth whitening composition for less than 5 seconds per application.

The invention also features a kit for tooth whitening including a tooth whitening composition of the im ention and an apparatus for preparing and/or apph ing the 25 composition.

The invention also features a kit for tooth whitening including a tooth whitening composition of the invention and instructions for determining a composition application time to achie\ e a desired w hitening effect.

The invention also features a method for tooth whitening including at least one 30 application of actinic light and a tooth whitening composition to at least one tooth such that the tooth is whitened at least about tw o shades w ith less than about 1 minute of total exposure to actinic light. In one embodiment, the tooth is whitened at least about three -3 - shades in less than about 30 seconds. In another embodiment, diere is no significant posttreatment sensitivit\. r- O (N σ3

BRIEF DESCRIPTION OF THE DRAWINGS

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Fig. 1 illustrates compositions of the present invention compared to other compositions containing other d\ es, before and after (see arrows) exposure to actinic light. 10

Fig, 2. illustrates compositions of the present invention compared to other compositions containing other dves. after a 5 h period folloA\ing extrusion of the compositions from a mixing syringe,

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In order to more clearh and conciseh describe the subject matter of the claims, the 15 follow ing definitions are intended to pro^ ide guidance as to the meaning of specific terms used in the follow ing w ritten description, examples and appended claims.

The term "accelerating agent" refers to an\ agent capable of accelerating aitd/or contributing to the completion of radical generation (e.g., sodium perborate).

The term "actinic light" refers to light energv' capable of being absorbed b>- an 20 activating agent.

The term "activating agent" refers to iuiy agent capable of absorbing actinic light. Preferably, the activating agent enhances and/or accelerates the dispersion of light energ\·, or otherwise enhances and/or activates the decomposition of an oxidizing agent. Activating agents include agents capable of absorbing light energv and emitting light 25 energv, e.g., fluorochromes. Suitable acti\ating agents include e.g,, Eosin. which refers to Eosin B. Eosin Y. or a combination thereof, and ErvtliiOsine B (also kno\\n as Er\ throsine).

The term "eosin" refers to fiuorescent red d> e resulting from the action of bromine on fluorescein. There are two veiy closeh related compounds commonly referred to as 30 eosin. Eosin Y is a tetrabromo derivative of fluorescein (also known as eosin Y ws, eosin yellowish. Acid Red 87. C.I. 45380. bromoeosine. bromofluoresceic acid, D&C Red No. 22); it has a veiy slightly yellowish cast. The other eosin compound, eosin B, is a dibromo -4- ο (N σ3 m

m IT) m o (N r- o (N derivative of fluorescein (eosin bluish. Acid Red 91, C.I. 45400, Saffrosine, Eosin Scarlet, or imperial red): it has a ^ eiv faint bluish cast.

The term "en throsine" refers to fluorescent cherr\ -pink fluorone food coloring. It is the disodiiim salt of 2.4.5,7-tetraiodofluorescein. It is also kno^^n as FD&C Red No. 3, 5 Food Red 14, and Acid Red 51. En throsine is also kno^xn as er> throsine B.

The term "oxidizing agent" refers to an\ agent capable of oxidizing, and also includes precursors of compounds capable of oxidizing. Examples of oxidizing agents include, but are not limited to. peroxide, peroxx acid, hydrogen peroxide, carbamide peroxide, alkali metal peroxides, alkali metal percarbonates. peroxx acetic acid, and alkali 10 metal perborates.

The term "post-treatment sensitivitx" refers to sensitivitx or instant pain experienced by a subject after a tooth xxhitening procedure. Sensitix itx can include, but is not limited to, stimuli such as temperature and pressure. Instant pain tx picallx occurs xxithoul stimuli. The terms "signiflcant sensitixilx" or "significant post-treatment 15 sensitivitx" and the like, refer to significant discomfort post-treatment, including sensitivitx and/or instant pain for more than four hours. The term "insignificant pain" refers to minimum sensitivitx' to stimuli such as temperature and/or pressure for less than four hours post-treatment.

The term "stabilizing agent" refers to anx agent tliat stabilizes one or more agents 20 of the composition fe.g., an oxidizing agent such as hx drogen peroxide). The stabilizing agent can act to stabilize the agent or agents against spontaneous or unxx anted reactix itx in use and/or in storage. Suitable stabilizing agents include sodium acetate. In some instances, the stabilizing agent can stabilize hydrogen peroxide for about one x ear.

The term "total exposure to actinic light" refers to the total lime a tooth is exposed 25 to actinic light including multiple applications of aclinic light over the course of a treatment session.

The term "transparent" refers to a composition capable of at least 70% transmission of light. The term "translucent" refers to a composition capable of at least about 40% transmission of liglit. The light referred to can be. eg., actinic light feg.,from a laser), 30 emitted light (e.g.. from a fluorochrome). or both.

The term "translucencx agent" refers to anx agent capable of increasing the translucencx of a composition. Such agents can increase translucency, e.g., upon addition to the composition, upon activation (e.g., b> heat, actinic light and/or emitted light), or both. ο (Ν m Ό ο (Ν ο (Ν

When ranges are disclosed herein (e.g.. waAelength. pH. concentration, paiticle sizes, and whitening ranges) all individual \ allies and ranges within tlie disclosed ranges 5 are regarded as part of and encompassed b\ the present in\ ention. All concentrations are pro\ ided in w eight % of the composition unless indicated otheni ise.

Where "a", "an" or the like is used herein, tliese articles are used in the open or non-restrictive sense, e.g., to indicate "at least one" or "one or more". Similarly, the term "or" is used in the open or nonrestrictive sense. /.<?., to mean "and/or." According!), the 10 terms "or" and "and/or" are used interchangeabh and are meant to have the same meaning.

In one aspect, the present imention proiides tooth whitening compositions that include an oxidizing agent (e.g., hi drogen peroxide), and an actiiating agent that has an emission waielength between about 400 nm and about 570 nm (e.g. Eosin B, Eosin Y, Er\ throsine B or combinations thereoO The composition can also include additional 15 agents including, but not limited to. pH adjusting agents, thickening agents, stabilizing agents, accelerating agents, gelling agents, translucenc) agents.

The oxidizing agent can be an> oxidizing agent known in the art. In one embodiment, the oxidizing agent includes Iw drogen peroxide or sodium perborate or both. Additional!) or alternatively, the oxidizing agent can include carbamide peroxide, alkali 20 metal peroxides, alkali metal percarbonates. alkali metal perborates or combinations of these compounds. The oxidizing agents can be. e.g. liquid, gel. or paste compositions capable of interacting with the activating compound w hen exposed to actinic light.

The concentration of the oxidizing agent can be varied in the present invention. In one embodiment, the oxidizing composition includes a h) drogen peroxide, e.g.. in a range 25 of about 1% to about 70%. In a further embodiment, the oxidizing composition includes about 50% h) drogen peroxide.

The activating agent can include an) agent with an emission waielengtli between about 400 nm and about 570 nm. In another embodiment, tlie actii ating agent emits light in the range of between about 435 nm and about 520 nm. In one embodiment, the 30 actii ating agent emits light in the range of between about 520 nm and about 565 nm. In certain embodiments, the agent both absorbs and emits light in the abo\ e ranges. In one embodiment, the actii ating agent emits green light. In another embodiment, the actii ating -6 ο (Ν α m m in Ό ο (Ν ο (Ν agent emits blue-green light, hi one embodiment the activating agent botli absorbs and emits green light.

In one embodiment, the activating agent includes at least one of Eosin B, Eosin Y, or Ervthrosine B or combinations thereof. In anotlier embodiment, the \ihitening 5 composition includes in the range of about 0.5% to about 0.8%, or betw een about 0.02% and about 1.2% or less than about 12% of at least one of Eosin B or Eosin Y or combinations thereof or from about 0,02% to about 12% {e,g„ 0.02-0.5%, 0.02-0.2%. 0.05-0,15%. 0.05-0,1%) of at least one of Eosin B or Eosin Y or combinations thereof In yet another embodiment, the composition includes about 0.02% to about 12% of Eosin B 10 or Eosin Y or combinations thereof ajid/or from about 0.01% to about 1%. or about 0.005% and about 0.15%. or from about 0.005% to 1% of Eiythrosine B. It is behei ed that the combination of Eosin B and/or Eosin Y and/or Eri throsine B has a si nergistic effect. It is believed this synergistic effect may be related to the close absorption peaks of the d\ es. It is further believed that because Eosin B and/or Eosin Y and Eiythrosine B reeniit 15 green light, that this green light can and ma> be further absorbed (or reabsorbed) b> the fluorochromes so that light energy is not dissipated as in conventional compositions. This absorbed and re-emitted light not only penetrates throughout the bleaching gel, but also is transmitted into the enamel and dentin. Dyes such as Eosin B and Eosin Y ai‘e also advantageous as they aie significantly less toxic than dy es such as Rliodamine B 20 Without wishing to be bound to any paiticular theoiv, it is belie\ed that because dentin and enamel transmit green light, liglit in this range can be transntitted into the dentin and/or enamel of the tooth, causing excitation of electrons in specific chemical bonds within the acti\ ating agent and tooth chromophores. making them more susceptible to be attacked by free radicals. The activating agents of the in\ ention can include blue-25 green and/or blue emitting dy es. Accordingly, the present in\ ention is based, at least in pai't. on the disco\ ery tiiat the use of the acti\ ating agents of the iiwention significantly enhance and/or contribute to the enlrancement of a whitening effect in a fraction of the lime required by conventional compositions. Because the teeth are only exposed to the whitening composition for a fraction of the time as compared to conventional teeth 30 whitening compositions, superficial cracks and crevices, caused by prolonged exposure to free radicals, can be reduced or eliminated. Because decalcification can occur in the cracks and cre\ ices caused by prolonged exposure to free radicals, stains more easily return as the -7 - decalcified enamel acts as a sponge. In the present in^ ention. the decreased exposure time to free radicals reduces the possibilitx' of crevices and cracks, thus leading to a significantly prolonged or permanent whitening effect for deeper pigments. Moreover, prolonged periods of exposure cause the enamel to become brittle. It is belie\ ed that the 5 composition and methods of the present in\ ention a\ oid compromise of the enamel. ο (N a

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In one embodiment, the activating agent or agents not only ai’e capable of emitting light in the rx avelength range from about 400 nm to about 570 nm. but also absorb light in the rwar elength range from about 400 nm to about 570 nm. Such an acti\ ating agent is activated b>· light in the \\aAelenglh range of from about 400 nm to about 570 nm. 10 Accordingly, in one embodiment the actiAating agent absorbs light in the ^^aΛelength range of about 400 nm to about 570 nm. In another embodiment, the actir ating agent absorbs light at a wa\ elength between about 470 nm to about 550 nm. This embodiment therefore allorv s for the optimal absorption of energ> from the actinic light and the optimal transmission through dentin and enamel. 15 Without wishing to be bound to aiw particular theon, it is also believed that acti\ ating agents of the present in\’ention. w hen exposed to actinic light, can accelerate the dispersion of light energy· which consequently leads to an instantaneous and complete photochemical activation of the peroxide within the gel. It is believed tliat the gel mass better transmits light in the w a\ elength range of about 400 nm to about 570 nm. so tliat 20 when an activating agent is exposed to actinic light, the dispersion of the light energy-leads to an accelerated photochemical activation of the peroxide. Together, these embodiments allow for optimal absorption by the activating agent of energy from the actinic light and the optimal transmission through the composition, dentin and enamel.

In one embodiment, the composition also includes a stabilizing agent. In one 25 embodiment, the stabilizing agent stabilizes the peroxide concentration in the composition for days, weeks, months, a year or se^eΓal year's. In one embodiment, the stabilizing agent not only stabilizes the oxidizing agent, but also is a pH modifier and/or stabilizer. In another embodiment, the stabilizing agent is sodium acetate. In one embodiment, sodium acetate is added until the desired pH is attained. In yet airother embodiment, the 30 composition includes between about 0.1% and about 50% stabilizing agent. Any value or range w ithin this range is meant to be encompassed. -8 ο (Ν α m m IT) cn Ο (Ν Ο (Ν Γ--

In one embodiment, the stabilizing agent is selected from the group consisting of antioxidants such as sodium sulfite, metal chelators (e.g.. EDTA). and stabilizers ie.g.. tin salts, phosphoric acid, and tin sulphonates). In some embodiments, the stabilizing agent scavenges or othen\ ise isolates or removes from solution, metal ions that can potentially 5 destabilize the hydrogen peroxide.

In one embodiment, the stabilizing agent is or includes sodium acetate fe.g, sodium acetate trihydrate). Sodium acetate has been found to inhibit spontaneous reactivity of h> drogen peroxide and therefore can provide impro\ ed stability.

In one embodiment, the pH of the composition is in or adjusted to the range of 10 from about 4 to about 10. In alkaline conditions, with a pH from about 8 to about 10, the stronger free radical, perhydroxy I ions, can be generated. Perhy droxy 1 free radicals are capable of reacting not only with yellow and brown stains but eAen with grey chroinophores situated deeper in the tooth stnicture. In further embodiments, the pH of the composition is between about 5 and about 7, or between about 5 and about 6. In certain 15 embodiments the pH is about 6.

Suitable pH adjusting agents include, but are not limited to. sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium carbonate, potassium carbonate, TRIS, and triethanolamine- or any other salt of an alkaline base w hich is safely used in the mouth. In another embodiment, the pH adjusting agent is sodium perborate. In certain 20 embodiments of the in\ ention. a single component may act as a pH adjusting agent or as a stabilizing agent or may ser\ e both functions. In one embodiment, sodium acetate acts as a pH adjusting agent and as a stabilizing agent. In further embodiments, the pH adjusting agent is of the group consisting of sodium bicarbonate, calcium bicarbonate, sodium carbonate and calcium carbonate. 25 Additionally or alternatively , the composition can include a thickening agent to impro\ e the ease of application of the composition to the teetli such that e\ en and effecti\ e coverage is more readily achieved. Suitable thickening agents include but aie not limited to mixed silica-aluminum oxides, long chain hy drocarbons such as sy nthetic carbomers {e.g., Carbopol), triethanolamine (e.g.,Trolamine). and water soluble poly (ethylene oxide) 30 resins fe.g., Polyox™). Suitable thickening agents also include amide starches.

It has been found that using an agent which has a particle size in the range from about 0,2 microns (pm) to about 0,7 μιη pro\ ides for more widespread dispersion of the -9- oxidizing agent on the particle surface. Accordingh , in one embodiment, the acti\ ating agent has a particle size below about 2 microns or beloAV about 1 micron. In other embodiments, the agent has a particle size below about 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, or 0.2 microns. In other embodiments, the activating agent has a particle size betw een about 0.1 5 and about 0.8, between about 0.2 and about 0.7, or between about 0.3 and about 0.6 microns. ο (N σ3

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Additionalh or alternativeh, the thickening agent can include fumed silica and/or aiw other inert inorganic material that ma\ be used as a cairier and can aid in tlie deli\ er\ of active oxygen to the tooth surface. Fumed silica of a small particle size (e.g., between 10 about 0.2 microns and about 0.4 microns), can provide efficient dispersion of Iw drogen peroxide and reflection of light energ> w ithin the oxidizing composition.

In some embodiments, the compositions of the in\ention include a reaction accelerator or accelerating agent. In one embodiment, the composition includes sodium perborate. Sodium perborate has selective reactivitv with h> drogen peroxide in forming 15 free radicals (reacts w ith w ater to release h> drogen peroxide). The use of one or more activating agents (e.g., sodium perborate) can be advantageous because the} can absorb and retain heat generated in the composition b>. e.g. actinic light, thus restricting an> such heat to ^e gel in order to accelerate tlie reaction without heating the tooth, which can cause sensiti\ it\. In addition, acceleration of the reaction means that the composition can 20 be remo\ ed more quick!} than con\ entional compositions thereb}' decreasing exposure of the patient to the composition and thus resulting in sensitivity and/or other damage to tissues aiTd teeth.

In one embodiment, the compositions of the in\ ention include betvx een about 0.8% and about 15%. or betw een about 0.3% and about 18% of accelerator agent. 25 In further embodiments, the compositions of the invention include a gelling agent.

Preferabl} tlie gelling agent is also a translucenc} agent. For example, a h}dropliilic gelling agent can be emplo} ed to increase the translucenc} of the resulting composition or gel.

In some embodiments, the nature of the gelling agent (e.g., its Iw drophilic nature) 30 pre\ ents \ aporization of the gel w hen exposed to actinic light, thus improving h} dration of the coated tooth area. Increased h}dration of the teeth and surrounding tissues is associated w ith decreased discomfort and sensitivit}. In one embodiment, the gelling agent - 10- ο (N a

m IT) Ό m o (N o (N t-· can include, for example, one or more modified starches and/or glucose. In one embodiment, modified starches and/or glucose are acti\ated in cold water. In some embodiments, the gelling agent further enhances the consistenc} of the composition, facilitating the application to the tooth surface. 5 The translucenc) agent can enhance translucenc\ or transparenc} upon addition to the composition and/or upon activation b>. e.g., actinic light, emitted light and/or heat. In one embodiment, it minimizes ^aporization of the composition. Additionally or alternati\ el\, the gelling and/or translucenc\ agent minindzes an> thermal effects b> absorbing any heat generated in the composition. 10 In one embodiment the composition is a translucent composition. In another embodiment the composition is a transparent composition. In certain embodiments, the composition is translucent or transparent to the actinic light it will be exposed to (e.g., green, blue-green or blue light).

In one embodiment, the composition includes an o.xidizing agent (e.g.. Iw drogen 15 peroxide), an accelerating agent (e.g., sodium perborate), an activating agent (Eosin B, Eosin Y , En throsine B or combinations thereof), a stabilizing agent (e.g. sodium acetate trihv drate), a pH adjusting agent, a thickening agent (e.g, fumed silica or silicon dioxide or both), and a gelling agent. In one embodiment, the pH of the composition is from about 6 to about 10. In some embodiments, the pH of the composition is from about 8 to about 20 10. In other embodiments, the pH of the composition is from about 4 to about 10.

Another aspect of the invention provides a method for tooth whitening including applying a tooth whitening composition of the present invention to at least one tooth, and exposing the tooth whitening composition to actinic light to activate the oxidizing agent. The composition mav be an\ of the compositions described herein. 25 In one embodiment, the method for bleaching the teeth is performed in a dentist's office or dental operatoiy under ordinaiy conditions. The composition can be mixed chair-side and applied to the surfaces of as manv· teeth as are desired to be whitened. Alternatively, the composition can be provided without the need for mixing chair-side. Thereafter, the composition can be exposed to actinic light to accelerate decomposition of 30 the oxidizing agent and the formation of free radicals. In one embodiment, premixes can be prepared w ith some or all of the ingredients and then mixed chair-side and applied to the teeth. In one embodiment, a hv'drogen peroxide/sodium acetate solution premix can be -11 prepared and stored prior to use. Additionally or alteraatiA ely, some or all of tlie remaining ingredients can also be separately premixed and stored prior to use. Such premixes can be stored, e.g., for at least about one year. ο (N a

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The compositions of the invention can be used to whiten teeth discolored b>’ any 5 agent or disorder. For example, the compositions may be used to A\hiten discoloration due to stains fe.g., tobacco, coffee, tea and/or food stains), fluorosis, developmental disturbances, bacteria, genetics, tetrac>cline antibiotics, trauma, blood decomposition, pigments present during de\ elopment of teetli. etc.

Aity source of aclinic light can be used and preferabh' it is capable of emitting light 10 in a wavelength appropriate to the activating agent employ ed in the composition. In one embodiment, e.g., an argon laser is used. In another embodiment, a potassium-titaiiyl phosphate (KTP) laser (e.g., a GreenLight^·^ laser) is used as a light source. In one embodiment the light source emits light at or near the absorption wa\elength of the acti\ating agent or at least one of the activating agents, if several are included in the 15 composition.

The most intense fluorescence (e.g., emission) from a fluorochrome d} e occurs A\hen it is irradiated with wa\ elengllis close to the peak of the absorption w a\ elength (i.e., excitation cur\ e). Accordingly, in one embodiment, the actinic light is at a wm elength of about the absorption w a\ elength of the acti\ ating agent. In one embodiment, tlie actinic 20 light has a wa\elength in the range from about 470 nm to about 550 nm. In another embodiment, the actinic light has a wavelength in the range from about 470 nm to about 520 nm. In >et another embodiment, an argon laser provides actinic light in the wax elength range from about 470 nm to about 520 nm. In a further embodiment, the actinic light has a wa\elength of about 530 nm to about 535 nm. In still another 25 embodiment, the source of actinic light is in the wa\ elength range of about 530 nm to about 535 nm is a KTP laser. In this embodiment the source is a KTP laser set at about 532 nm. In anotlier embodiment, a photocuring de\ ice is tlie source of actinic light.

In one embodiment, the tooth is exposed to actinic liglit for less than 20 minutes, in another for less than 10 minutes, in another for less than 5 minutes. In one embodiment the 30 tooth is exposed to actinic light for less than 4, 3, 2. or 1 minute. In one embodiment, the imention pro\ ides a method for whitening teeth at least 2 shades in about 1 minute. In - 12- some embodiments, there is no significant post- treatment sensiti^’it^. In other embodiments, there is no post-treatment sensiti\ it>·.

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In one embodiment, the tooth whitening composition is applied and the tooth is exposed to multiple applications of actinic light, for a time of about 4 to about 6 seconds 5 each tooth per exposure. In some embodiments, the tooth is exposed to actinic ligltt at least tw o, three, four. fi\ e or six times. In some embodiments, a fresh application of the tooth whitening composition is applied before each exposure to actinic light. In some embodiments, the total exposure to actinic light is less tlian about one minute. In other embodiments, the total exposure to actinic light is less than about 60, 40, 30, or 20 10 seconds.

In one embodiment, the tooth is whitened at least 7 shades. 6 shades. 5 shades, 4 shades, 3 shades, 2 shades or 1 shade. Shades can be determined before and after treatment using any of a number of shade guides, including, e.g., the VITA r· (Vita Zahnfabrik H. Ranter GmbH &amp; Co., KG). CHROMASCOPR {Ivoclar Vivadent. Inc.) or BIODENT 15 (Dentsply Intenational) shade guides. Optionalh. a shade taking s>stem. e.g., the

ShadeEx e NCC Dental Chroma Meter, can be emplox ed to determine shade before and/or after treatment.

In one embodiment, the toodi is whitened at least two shades, three shades, four shades, fix e shades, six shades or sex en shades in less than about one minute of total 20 exposure time to actinic light. In some embodiments, the tooth is xxhitened at least two shades, three shades, four shades, fixe shades, six shades or sex en shades in less than about 40 seconds of total exposure time to actinic light. In some embodiments, the tooth is whitened at least hxo shades, three shades, four shades, five shades, six shades or seven shades in less than about 30 seconds of total exposure time to actinic light. In some 25 embodiments, the tooth is xxhitened at least txxo shades, three shades, four shades, five shades, six shades or seven shades in less than about 20 seconds or ex en less than about 10 seconds of total exposure time to actinic light.

In one embodiment, the risk of transient inflammation of the pulp bx percolation of hxdrogen peroxide is reduced, not significant and/or eliminated. Without xxishing to be 30 bound bx any particular theorx, inflammation of the pulp is thought to be caused bx percolation of hxdrogen peroxide into the pulp tissue. In some embodiments, the sx nergistic effect of the actix ating agents (e.g., Eosin B and/or Eosin Y and/or Erx throsine - 13- ο (Ν α m m m Ο (Ν ο (Ν Β) and the actinic light results in an instantaneous and complete photochemical reaction. Accordingh. exposure of the tooth, the pulp, and/or the surroiuidiiig tissues to the oxidizing agent and/or other components in the composition is dramaticalh reduced.

In \et another aspect, the in^ention pro\ides a method for tooth ^^hitening 5 comprising application of actinic light and a composition of tlie invention (an> of the compositions described herein) to at least one tooth such that tlie tooth is whitened at least about two shades in less than about 10 minutes. In another embodiment, the tooth is i\hitened at least about tw o shades in less than about 5 minutes, less than about 4 minutes, less than about 3 minutes, less than about 2 minutes or in about 1 minute. In some 10 embodiments, the teeth are whitened at least about 3 shades. 4 shade or 5 shades. In some embodiments, there is no significant post-treatment sensiti\it>' or no post-treatment sensitivity'.

In yet another aspect, the invention provides a kit for preparing or applying a tooth whitening composition in accordance ^\ith the present in^ ention. In one embodiment, the 15 kit includes an oxidizing agent and an actiA ating agent that has an emission wa^ elength between about 400 nm and about 570 nm. The composition can be an\ of the compositions of the present invention. In one embodiment, the composition is not combined, and may optionally include an apparatus to combine tw o or more components or preniixes of the composition. In anotlier embodiment the composition does not require 20 any combination f/.c., it is ready to use and does not require any pre-mixing chair-side).

In another embodiment, the kit includes a composition of the invention and directions for application. Additionally or alternatively, the kit can include an apparatus for application fe.g., brushes or tray s or both). The kit can also include charts or other information helpful in assessing the whitening effect desired and/or achieved by the 25 methods and compositions of the invention. The kit can also include a source of actinic light.

Identification of equi\alent compositions, methods and kits are well within the skill of the ordinan' practitioner and w ould require no more than routine experimentation, in light of the teachings of the pr^ent disclosure. Practice of the invention w ill be still 30 more fully understood from the following examples, which are presented herein for illustration only and should not be construed as limiting the invention in any way. - 14- Γ-- ο (Ν σ3 m m IT) Ό m Ο (Ν τ-Η Ο (Ν 10 15 EXAMPLE 1 Preparation of an Exemplary Whitening Composition and Activation by Actinic Light A preniix \\ as prepared b\ mixing 4 mg of Eosin B, 1 mg of En throsine B, 450 mg of fumed silica, and 45 mg of sodium perborate. Separateh, the pH of a 50% h\ drogen peroxide solution \A as adjusted to pH 6 using sodium acetate solution. Approximateh’ 4-6 ml of the adjusted hydrogen peroxide solution nas then added to the premix in a plastic mixing chamber and immediateh· applied. The gel was applied to frontal surface of the teeth of each subject beginning from the frontal ajiterior incisors, followed by the posteriors, and finall> the posterior incisors. The gel w as acti\ ated b\ a KTP laser set at a continuous wa\ e of 0.5 w atts. The laser w as applied to each tooth for 2-3 seconds. During tliis time, the gel turned from orange-red to transparent and erentualh became dull. After 3-4 minutes for two full arches from preniolar to premolar, tlie gel rvas aspirated, and the teeth were lighth scrubbed with a cotton roll to clean the surface of the enamel. A second coaling of gel was applied using fresh gel and acti\ated with the KTP laser as described above. Up to six consecutive applications w ere performed to achieve the desired whitening effect for each patient. The duration of the sessions K picalK' did irot exceed 40 minutes. 20 EXAMPLE 2

Whitening Effect of Composition A comparative study was conducted on 10 volunteers between an exemplaiy composition of the present invention and the SMARTBLEACH laser teeth whitening s> stems, which is a composition comprising Rhodaniine B and Iw drogen peroxide. The 25 shade of each patient's teeth Avas recorded prior to application of w hitening composition.

Teeth were coated with the composition prepai'ed in Example 1 and exposed to actinic light from a green laser set at 532 nm for one minute for the eiitire mouth (4-5 seconds per tooth) and then the composition was removed. The comparatiA e composition A\as applied to the teeth and exposed to light from a green laser set at 532 nm for 30 30 seconds per tooth and then left on the surface of the tooth for 10 minutes, in accordance A\ith the manufacturer instructions proA'ided AAith the composition. The comparatiAe composition required at least 3 to 4 applications, for a total duration of about 1.5 hours for - 15- ο (N σ3 m m ίΤ) Ό cn Ο (Ν Ο (Ν 10 the entire mouth. The composition was removed from each \ olunteer and the teeth were irrigated with water. The teeth were then 6λ aluated using tlie VITA scale for the whitening effect of the compositions. Patients were also e\ aluated for an\ post-treatment sensitiA ih b> asking them to rate the leA el of pain experienced, if an\.

The SmartbleachT'^ treatment resulted in a shade change of one to two shades in the > ellow group, while the exemplaiv composition of the present invention resulted in a shade change of 5 shades in the yellow group, e.g., Aj to Bi VITA scale. In the "\ ellow group"(A4-Ai). treatment witli the exemplan composition of the present invention resulted in shade changes of 4-5 shades, resulting in shades in the "white group" (Bi- B2). Treatment with the exemplatv composition for teeth in the "gre> " (C4-C1) and "gre>-brow n" (D4-D2) groups show ed changes of 2-3 shades in the first session.

The following 6λ aluation scale of post-sensitivit> w as used:

Level 0 No sensiti\ it> to thermal stimuli or an\ kind of pain follow ing treatment. Level 1 Sensitivity to thermal stimuli that lasts for a few seconds. Level 2 Pain or discomfort that occurs due to thermal stimuli and lasts for more than one minute. Optional pain treatment w ith analgesics. Level 3 Pain or discomfort that occurs automatically, requiring use of analgesics to control the pain.

Following treatment with the Smartbleach™ s> stem, all ten subjects experienced 15 pain from Le^ el 1 to Le\ el 3. Follow ing treatment w ith the exemplaiy composition of the present invention, nine subjects experienced no pain fe.g., Level 0), and onh one subject experienced pain of Level 1. EXAMPLE 3 20 Effect of Actinic Light Source A stud\ w as conducted on 28 \ olunteers comparing the effect of different actinic light sources in w hitening w ith the composition of Example 1. A proplw lactic session w as performed on each patient 3-4 da> s before the bleaching session. The shade of each patient's teeth w as recorded prior to application of w hitening composition. 25 Teeth were coated with the composition prepared in Example 1 and exposed to different sources of actinic light: a green laser (KTP) at 532 nni. a blue-green (argon) laser - 16- r- O (N a CT)

m Ό m o (N C-' O (N at 480-514 niiL a photo curing halogen lamp, and a LED photocuring device. The acti\ ation \\ a$ perfornied in the different patients for the left or the right sides of their dental arches according to an activation randomization mode. Specifically, a first patienfs right side \\ as ηςίίλ ated A\ith tlie 532 nm green laser, \\ hile the left side w as activated λ\ ith 5 the 480 nm - 514 nm bliie-green laser. A second patient's right side was acti\ ated w ith the photocuring halogen lamp, while the left side was activated with the LED photo curing device. A third patienfs right side was activated with the 532 nm green laser, while the left side was acti\ ated with the photocuring halogen lamp. A fourth patient's right side was activated with the 532 nm green laser, while the left side was activated with the LED 10 photocuring device. A fifth patient's right side was activated with the 480 nm - 514 nm blue-green laser, while the left side was acti\ ated with the photocuring halogen lamp. A sixth patient's right side Λ^as activated witli the 480 nm - 514 nm blue-green laser, wliile the left side w as activated w ith the LED photocuring de\ ice.

The composition w as renlo^ ed from the teeth of each \ ohuiteer and tlie teeth w ere 15 irrigated w ith w ater. The teeth w ere then e\ aluated using the VITA scale for the whitening effect of the compositions.

Activation b\ different photocuring devices produced comparable results. The speed of acti\ ation w ith the green laser and the blue-green laser w as 4-5 seconds per tooth, while the speed of activ ation with the photo curing devices w as about 10 seconds per 20 tooth. Accordingiv’, a whitening session emplov ing the green laser or the blue-green laser for the entire mouth would typically take approximateh' 30 minutes, and a session with a photocuring device would rt picalh’ take approximateh' 40 minutes. EXAMPLE 4 25 Preparation of composition

Teeth w hitening compositions w ere prepared according to the following table: - 17 ο (N a cn

Όo (N O (N

Table 1 Description Present Invention Prior art Activating I. Eosin Y (0.7 mg/g) 4, Acid Red 388 (0.7 mg/g) 5 Acid Red 92 (0 7 mg/g) 2. Ely throsine B (0.7 mg/g) 6. Acid Red 388 &amp; Acid Red agent 3. Eosin Y &amp; En throsine B 92 (both 0.7 mg/g) 7. FD&amp;C Red 40 (0.7 mg/g) (both 0.7 mg/g) Common - Hydrogen peroxide components - Silica - Starch (Photoactive - Sodium perborate booster) - Sodium Acetate - Distilled w ater EXAMPLE 5 5 Clinical assessment of light absorption and quantitative nieasiireinent of fluorescence emission

Samples of each teeth ^\hiteiiing composition described in Table 1 ^^ere extruded from a s> ringe after mixing, and a portion of each extinded sample w as exposed to actinic light for 60 seconds, while the remainder was not. Visual assessment of the change in 10 color was performed and a photograph of tire composition was taken immediateh- after light exposure.

As shown in Fig. 1, prior to exposure to actinic light, all compositions displa> ed a deal’ and distinct coloring according to the d\ e used in the composition. During exposure to actinic light, the compositions of the present invention markedh fluoresced, as did the 15 compositions containing the Acid Red d> es. but the composition containing FD&amp;C Red 40 appeared non-fluorescent (results not shoA\n). Following actinic light exposure, the coloring of the compositions of the present in\ ention distinctly changed: the composition containing eosin Y alone turned a pristine white, while the composition containing en throsine B and eosin Y + er\ throsine B turned a bluish color. The compositions 20 containing Acid Red 388 or Acid Red 92 alone, or a mixture of these tw o d> es did not change color. Lasth the compositions containing FD&amp;C Red 40 was also unchanged. Thus, onh the compositions of the present invention displa> ed an\ robust photochemical bleaching reactions. - 18-

ο (N

cn m o (N r- o (N 10 15 t-·

Fig. 2 shows that following actinic light exposure, all tliree of the compositions of the present in\ention became soft and moist, and collapsed into single mass of composition. Tlie addition of sodium acetate to the gel composition accelerated the acti\ ation of the gel w hen exposed to actinic light. This acceleration ma\ be caused by the increase in pH of the photoactive booster. Gas bubbles w ere observ ed emerging from the samples. This observation is consistent w ith a rapid and robust decomposition of hydrogen peroxide into water and oxygen (as per the known reaction: 2 —* 2 HiO + O2) accelerated b\ the dispersion of light energ} in the composition b>· the activating agents. The other sample compositions did not mix into a single mass, but rather presen ed a more solid texture, with strand-like aspects, as generated during extrusion from the svringe. As shown in Fig. 2, a second v isual assessment was performed after the compositions had been left unattended for 5 hours at room temperature. Interestingh, the compositions of the present inv ention remained moist and show ed evidence of gaseous releases, w hile the other compositions had hardened after tlris period. Tliese results suggest that the compositions of the present invention are able to cause an accelerated photochemical activation of the hv drogen peroxide present in the composition. None of the other tested compositions displayed comparable results. EXAMPLE 6 20 Teeth whitening results

Compositions containing eosin Y and erv throsine B, and compositions containing Acid Red 388 alone. Acid Red 92 alone and FD&amp;C Red 40 alone vvere prepared as in Table 1 abov e. Each of tire sample composition w as directlv- and simultaneouslv tested on the teeth of a human subject. The mouth of each subject was div ided in 4 quadrants 25 (upper-left, lower-left, upper-right, and lower-right). To maintain a fixed optical position to assess teeth whitening, the composition of the present inv ention was in each case applied to the riglit quadrants, while the cornparativ e composition w as applied to the left quadrants. The compositions were exposed to actinic light (a Blue Phase LED photo curing device) for 20 seconds per tooth. The effect of each composition was scored 30 according to the Vita R Brightness scale and results are show n in Table 2. - 19- ο (Ν α m m IT) mο (Ν r- Ο (Ν

Table 2 Patient Right quadrant Vita shade conversion Left quadrant Vita shade conversion 1 Eosin Y and Ely throsine B A3 to Al (7shades) Acid Red 388 A3 to A2.5 (>3 shades) 2 Eosin Y and Ely throsine B A3 to Al (7shades) Acid Red 92 No change 3 Eosin Y and Ely throsine B A3 to Al (7shades) FD&amp;C Red 40 No change

Comparative results of teeth whitening using the composition of the present invention and compositions containing Acid Red dyes or FD&amp;C Red 40 5 Vita® Brightness scale B1 = lightest shade C4 = darkest shade B1 Al B2 D2 A2 Cl C2 D4 A3 D3 B3 A3,5 B4 C3 A4 C4 1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 10

For each of the three patients treated, use of the composition of the present invention resulted in a significant improvement of 7 shades (A3 to Al), while the composition containing Acid Red 388 caused a modest improvement slightK' better than 3 shades (A3 to A2.5), Compositions containing Acid Red 92 or FD&amp;C Red 40 had no effect whatsoe\ er. Thus, the composition of the present in\ ention is the most efficient teeth whitening composition. 15 20

The scientific results aboA e show that based on exposure to actinic light, the red dyes used in the composition of the present invention are more readily acti\ ated. Also, these scientific results show that under the teeth whitening conditions of 20 seconds per teeth, use of Acid Red 388, Acid Red 92. or FD&amp;C Red 40 do not result in a teeth w hitening effect as potent as that of the composition of the present invention. In fact. Acid red 92 and FD&amp;C Red 40 aio unable to cause any teeth i\hitening effect under the conditions used. These results indicate tliat these d\ es do not contribute as efficienth (if at all) as eosin Y or eiythrosine B. to a teetli whitening effect. EXAMPLE 7 Teeth whitening results

Compositions containing eosin Y alone, en ihrosine B alone, both eosin Y and 25 eiy throsine B, and compositions containing Acid Red 388, Acid Red 92 alone or in combination, and FD&amp;C Red 40 w ere prepared as Example 4 aboA-e. Each of the sample -20- ο (N σ3

Ό o (N o (N composition w as directl\ tested on tlie teeth of a human subject. The compositions \\ ere exposed to actinic light (a Blue Phase LED photo curing device) for 20 seconds per tooth. The effect of each composition was scored according to the Vita R Brightness scale and results are shown in Table 3.

Comparative results of teeth whitening using the composition of the present invention and compositions containing Acid Red dyes or FD&amp;C Red 40

Table 3

Patient Dyes Vita® shade conversion 1 Eosin Y and eiythrosine B A3 to AI (7 shades) 2 Eosin Y alone A3 to A1 (7 shades) 3 Eiythrosine B alone A3 to C2 (2 shades) 4 Acid Red 388 A3 to A2 (4 shades) 5 Acid Red 92 No change 6 FD&amp;C Red 40 No change 7 Acid Red 388 and Acid Red 92 A3 to A2 (4 shades)

Vita® Brightness scale B1 = lightest shade C4 = darkest shade B1 Al B2 D2 A2 Cl C2 D4 A3 D3 B3 A3.5 B4 C3 A4 C4 1 2 T 3 4 5 6 7 8 9 10 11 12 13 14 15 16 10

For each of the diree patients treated, use of the composition of the present invention containing eosin Y alone or eosin Y and er\ throsine B resulted in a significant improvement of 7 shades (A3 to Al). while the composition containing Acid Red 388 15 alone or in combination w ith acid red 92 caused a modest improvement slightK better than 3 to 4 shades (A3 to A2.5 or A2). Compositions containing Acid Red 92 alone or FD&amp;C Red 40 alone had no effect w hatsoe^ er. Thus, the composition of the present in\ ention is the most efficient teeth whiteiring composition.

The scientific results abo\ e show Uiat based on exposure to actinic light, die red 20 d\ es used in the composition of the present invention are more readih actii ated. Also, these scientific results show that under the teeth whitening conditions of 20 seconds per teeth, use of Acid Red 388, Acid Red 92. or FD&amp;C Red 40 do not result in a teedi -21 - Γ-- ο (Ν λΛ hiteriing effect as potent as that of the composition of the present iiiA ention. In fact. \\ hen used alone. Acid red 92 and FD&amp;C Red 40 are unable to cause any teedi whitening effect under the conditions used. These results indicate that these d\es do not contribute as efficiently (if at all) as eosin Y or eiythiOsine B, to a teeth whitening effect.

Όo (No (N -22·

Claims (13)

1. CLAIMS:

   1. A tooth whitening composition for whitening a tooth in vivo in the gingiva of a patient, the tooth whitening composition comprising: an oxidizing agent; Eosin Y; and an accelerating agent, a stabilizing agent, or both.
2. 2. The composition according to claim 1, wherein the composition comprises a thickening agent.
3. 3. The composition according to claim 1 or 2. w herein the thickening agent is silicon dioxide and/or fumed silica having a particle size less than one micron.
4. 4. The composition according to any of claims 1-3. wherein the composition comprises a hydrophilic gelling agent.
5. 5. The composition according to any of claims 1-4. wherein the pH of the composition is betw een about 4 and about 10.
6. 6. The composition according to any of claims 1-5. w herein the composition is used for whitening a tooth in vivo in (he gingiva of a patient.
7. 7. A method for whitening a tooth in vivo in the gingiva of a patient, the method for tooth whitening consisting of: applying to at least one tooth a tooth whitening composition comprising: an oxidizing agent: and Eosin Y; and exposing the tooth whitening composition to actinic light for a period between 5 seconds and 10 minutes.
8. 8. The method according to claim 7. wherein the tooth is exposed to light for a period between 5 minutes and 10 minutes.
9. 9. The method according to claim 7 or 8. wherein the tooth is exposed to the tooth whitening composition for less than 5 seconds per application.
10. 10. The method according to any of claims 7-9. w herein the tooth is exposed to light for a period of 1 minute.
11. 11. The method according any of claims 7-10. w herein the tooth is exposed to light for a period of 30 seconds.
12. 12. A kit for tooth w hitening comprising: a composition according to claim 1: and an apparatus for applying the composition.
13. 13. A kit for tooth whitening comprising: a composition according to claim 1; and instructions for determining a composition application time to achieve a whitening effect.