TOOTH REMINERALIZATION

Abstract

An oral treatment device (10) for stimulating deposition of calcium phosphate from an amorphous calcium phosphate formulation in contact with a tooth (1) in an oral cavity is disclosed. The device comprises a first electrode (12) and a second electrode (14) spatially separated from the first electrode, wherein both the first electrode and the second electrode are arranged to contact the amorphous calcium phosphate formulation when the first electrode is arranged proximal to the tooth during use of the device; and the second electrode comprises a sacrificial material at least on its surface. Also disclosed is a kit of parts comprising the oral treatment device (10) and an ACP formulation and a method (100) for remineralizing a tooth using an amorphous calcium phosphate formulation.

Claims

1. An oral treatment device for stimulating deposition of calcium phosphate from an amorphous calcium phosphate formulation in contact with a tooth in an oral cavity, the device comprising a first electrode a second electrode spatially separated from the first electrode, and a power source coupled to the first electrode and the second electrode such that, during use of the device, the first electrode acts as a cathode and the second electrode acts as an anode, wherein: both the first electrode and the second electrode are arranged to contact the amorphous calcium phosphate formulation when the first electrode is arranged proximal to the tooth during use of the device; the second electrode comprises a sacrificial material at least on its surface, and wherein the power source is arranged to apply a potential difference across the anode and the cathode, which potential difference is sufficient to cause: a pH increase at the cathode through the formation of hydroxide anions; and the formation of cations of the sacrificial material at the anode.

2. The oral treatment device of claim 1, wherein the sacrificial material is zinc or a zinc alloy.

3. The oral treatment device of claim 1, wherein the first electrode is a brush electrode.

4. The oral treatment device of claim 3, wherein the brush electrode is made of carbon.

5. The oral treatment device of claim 1, further comprising a reservoir for containing the amorphous calcium phosphate formulation.

6. The oral treatment device of claim 5, wherein the first electrode and the second electrode at least partially contained within the reservoir.

7. The oral treatment device of claim 5, wherein the reservoir is a dental tray comprising a plurality of the first electrodes and a plurality of the second electrodes arranged in pairs of electrodes each comprising one of the first electrodes and one of the second electrodes, each pair of electrodes being arranged to stimulate deposition of calcium phosphate from the amorphous calcium phosphate formulation on a different tooth within the oral cavity.

8. The oral treatment device of claim 7, wherein the dental tray is made of an elastomeric material.

9. The oral treatment device of claim 1, wherein the oral treatment device is an applicator having a nozzle fluidly coupled to a coupling member arranged to interface with a reservoir wherein the first electrode is arranged proximal to an orifice of the nozzle and the second electrode is arranged upstream from the first electrode on the nozzle.

10. The oral treatment device of claim 1, wherein the oral treatment device is an electric toothbrush or an oral irrigator.

11. The oral treatment device of claim 1, wherein the potential difference is in a range of 0.5-2 V.

12. A tooth remineralization kit comprising the oral treatment device of claim 1 and an amorphous calcium phosphate formulation.

13. The tooth remineralization kit of claim 12, wherein the amorphous calcium phosphate formulation is a single phase formulation preferably having a pH in a range of 4-6.

14. A method for remineralizing a tooth using an amorphous calcium phosphate formulation, the method comprising: applying the amorphous calcium phosphate formulation to the tooth; contacting the applied amorphous calcium phosphate formulation with a first electrode proximal to the tooth and a second electrode, the second electrode comprising a sacrificial material at least on its surface; and applying a potential difference across the first electrode and the second electrode causing an increase in pH at the first electrode though the formation of hydroxide anions and the formation of cations of the sacrificial material at the second electrode.

15. An amorphous calcium phosphate formulation for use in a remineralizing treatment of a tooth comprising applying the amorphous calcium phosphate formulation to the tooth; contacting the applied amorphous calcium phosphate formulation with a first electrode proximal to the tooth and a second electrode, the second electrode comprising a sacrificial material at least on its surface; and applying a potential difference across the first electrode and the second electrode causing an increase in pH at the first electrode though the formation of hydroxide anions and the formation of cations of the sacrificial material at the second electrode.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Embodiments of the invention are described in more detail and by way of non-limiting examples with reference to the accompanying drawings, wherein:

[0029] FIG. 1 is a scanning electron microscope image of dentin;

[0030] FIG. 2 is a scanning electron microscope image of carious enamel;

[0031] FIG. 3 schematically depicts a cross-sectional view of an oral treatment device according to an embodiment;

[0032] FIG. 4 schematically depicts a perspective view of an oral treatment device according to another embodiment;

[0033] FIG. 5 schematically depicts a cross-sectional view of an oral treatment device according to yet another embodiment;

[0034] FIG. 6 schematically depicts a cross-sectional view of an oral treatment device according to yet another embodiment;

[0035] FIG. 7 schematically depicts a cross-sectional view of an oral treatment device according to yet another embodiment;

[0036] FIG. 8 is a flowchart of a method according to an embodiment; and

[0037] FIGS. 9-11 are images depicting experimental results demonstrating proof of concept of the present invention.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0038] It should be understood that the Figures are merely schematic and are not drawn to scale. It should also be understood that the same reference numerals are used throughout the Figures to indicate the same or similar parts.

[0039] FIG. 3 schematically depicts an oral treatment device 10 according to an embodiment. In this embodiment, the oral treatment device 10 is an applicator that can be positioned over at least one tooth 1 to be treated with an ACP formulation, e.g. because the tooth 1 exhibits the onset of caries defect 3. Of course, the tooth 1 may be treated for a number of reasons, e.g. to counter tooth sensitivity, such as tooth sensitivity resulting from a tooth whitening treatment or from enamel erosion through prolonged exposure to acid environments. The applicator typically contains a first electrode 12 arranged to be located in close proximity to the tooth 1 to be treated. The first electrode 12 preferably contacts the tooth 1. In order to achieve a large contact area between the first electrode 12 and the tooth 1, the first electrode 12 advantageously may take the shape of a brush electrode, which may be made of any suitable material. A particularly suitable material is a carbon-based material such as graphite.

[0040] The applicator further comprises a second electrode 14 that is spaced apart from the first electrode 12 such that a short-circuit between the first electrode and the second electrode 14 is avoided. The second electrode 14 may be located in any suitable location within the applicator. For example, the second electrode 14 may be positioned such that the tooth 1 is located in between the first electrode 12 and the second electrode 14, or may positioned such that the tooth 1 is outside a direct path between the first electrode 12 and the second electrode 14, e.g. the first electrode 12 is positioned in between the second electrode 14 and the tooth 1. More generally, the second electrode 14 may be located further away from the tooth 1 than the first electrode 12. For reasons explained in further detail below, the second electrode 14 contains a sacrificial material at least on its surface, that is, the second electrode 14 is coated with a sacrificial material or is formed of such a sacrificial material. Any suitable sacrificial material may be used for this purpose, and non-limiting examples of suitable sacrificial materials include magnesium, aluminum and zinc. Zinc (and zinc alloys) are particularly suitable because zinc cations are known to have an antimicrobial effect, such that the generation of such zinc cations in the vicinity of the tooth 1 can assist in killing harmful bacteria present on or in the tooth 1, e.g. in the caries defect 3.

[0041] The first electrode 12 and second electrode 14 are located in a reservoir 15 of the applicator for containing the ACP formulation such that both the first electrode 12 and the second electrode 14 contact the ACP formulation when loaded into the reservoir 15 of the applicator. During use of the applicator, the first electrode 12 and the second electrode 14 are conductively coupled to a power source (not shown) such as a battery or the like such that the first electrode 12 acts as the negative electrode (cathode) and the second electrode 14 acts as the positive electrode (anode). The power source may form an integral part of the applicator or may be attached to the applicator prior to use, e.g. through leads (not shown) extending from the applicator, which each lead being conductively coupled to one of the first electrode 12 and the second electrode 14. The power source creates a potential difference across the first electrode 12 and the second electrode 14 that triggers the following electrochemical half-reactions in case of the second electrode 14 comprising Zinc as its sacrificial material:

2H.sub.2O(1)+2e.sup.−H.sub.2(g)+20H.sup.−−0.8277V(Cathode)

Zn.sup.2+(aq)+2e.sup.−Zn(s) −0.7618 V (Anode)

[0042] Of course, the anode half-reaction may involve other sacrificial materials instead as will be readily understood by the skilled person. Generally speaking, any biocompatible sacrificial material that has a standard electrode potential lower than that of water for its redox reaction may be used for the second electrode 14 in the oral treatment device 10. The water hydrolyzed at the first electrode may come from any suitable source, e.g. water contained in the ACP formulation.

[0043] Importantly, the use of a sacrificial material for the second electrode 14 causes this material to become a reagent in the electrochemical half-reaction at the second electrode 14, thereby promoting the formation of cations of the sacrificial material and suppressing the formation of protons (H.sup.+ ions) from water hydrolysis. This therefore suppresses the unwanted recombination of hydroxide anions and protons into water molecules, which would counter the pH increase at the first electrode 12 by the generated hydroxide anions, which pH increase is required to increase the precipitation rate of calcium phosphate in or on the tooth surface. Moreover, the generation of protons is generally undesirable as acidic conditions should be avoided within an oral cavity, as such acidic conditions can cause enamel erosion as is well-known per se.

[0044] Another advantage of the use of a sacrificial material for the second electrode 14 is that the electrochemical reaction will commence at very low voltages, e.g. 0.1V, although voltages of above 0.5V are preferred to ensure sufficient deposition rates of the calcium phosphate. In an example embodiment, the power source is arranged to create a potential difference across the first electrode 12 and the second electrode 14 in a range of 1-2 V, thus ensuring a long continuous operation time in case of the power source comprising one or more batteries as well as minimizing the risk of the user of the oral treatment device 10 experiencing any discomfort.

[0045] Preferably, the potential difference is applied across the first electrode 12 and the sacrificial second electrode 14 of the oral treatment device 10 after a short delay following application of the ACP formulation onto the tooth 1 to allow diffusion of calcium, phosphate and, if present in the formulation, fluoride ions into the porous structures of the tooth 1. Such ion transport may be effected by passive diffusion, e.g. over a period of a few minutes, or by active delivery. For example, where the first electrode 12 and the second electrode 14 are arranged in a suitable configuration, iontophoresis may be applied using these electrodes to invoke such ion transport prior to the commencement of the aforementioned electrochemical reaction to stimulate calcium phosphate precipitation. Other suitable active ion transport techniques will be apparent to the skilled person.

[0046] The applicator may be made of any suitable material. Preferably, the applicator is made of an elastomeric material, e.g. a rubber-like material such as a silicone-based elastomer such that a malleable applicator is provided that can be easily molded to fit the shape of the tooth 1. Depending on the viscosity of the ACP formulation, the applicator may not be fully closed, as this for instance is unnecessary when the ACP formulation is highly viscous. In an embodiment, the oral treatment device 10 in the form of an applicator is a dental tray as schematically depicted in FIG. 4. The dental tray may comprise a plurality of first electrodes 12, e.g. arranged on a first wall section 16 of the dental tray and a plurality of sacrificial second electrodes 14, e.g. arranged on a second wall section 18 of the dental tray opposing the first wall section 16. Of course, other electrode arrangements, e.g. where the second electrodes 14 are arranged on a bottom section 19 of the dental tray, which bottom section 19 connects the first wall section 16 to the second wall section 18. The reservoir 15 is typically enclosed by the first wall section 16, the opposing second wall section 18 and the bottom section 19 of the dental tray. It should be understood that these sections may not be discrete portions of the dental tray, i.e. the dental tray may be a molded device, e.g. molded from an elastomeric material as previously explained.

[0047] The plurality of first electrodes 12 and the plurality of sacrificial second electrodes 14 may be arranged in electrode pairs with each pair consisting of a first electrode 12 and a second electrode 14 arranged to treat one of the teeth to be fitted into the dental tray such that each tooth 1 is aligned with one of these electrode pairs. The power source (not shown) may be arranged to address each of these pairs simultaneously or alternatively may be configurable to address individual electrode pairs, e.g. where specific teeth are targeted. To this end, a control device (not shown) for controlling the power source may visualize the teeth to be fitted into the dental tray such that a user of the control device can select the teeth to be treated, which user selection is translated by the control device into a control instruction to select the electrode pairs corresponding to the selected teeth such that ACP precipitation is stimulated at the selected teeth only by selective application of the potential difference across the electrode pairs associated with the selected teeth.

[0048] FIG. 5 schematically depicts another example embodiment of an oral treatment device 10 in the form of an applicator. In this embodiment, the applicator is a handheld device comprising a body containing the reservoir 15, which reservoir 15 is fluidly connected to a nozzle 40 having an orifice 42 through which the ACP formulation within the reservoir 15 can be applied to the patient's teeth. The ACP formulation may be forced from the reservoir 15 through the nozzle orifice 42 by a pump 32, e.g. a manual pump that can be activated by digit pressure such as thumb pressure. The pump 32 may activate a switch 34, which in turn activates a controller 36 controlling the delivery of a potential difference from the power source 50 across the first electrode 12 and the sacrificial second electrode 14 that are both arranged proximal to the nozzle orifice 42. The first electrode 12 typically extends further away from the nozzle 40 than the second electrode 14, i.e. the second electrode 14 is arranged upstream to the first electrode 12, such that the first electrode 12 may contact the surface of a tooth to be treated whilst the second electrode, whilst still in contact with the deposited ACP formulation is further away from the tooth to be treated than the first electrode 12.

[0049] Although the oral treatment device 10 in preferred embodiments is an applicator, more preferably a dental dray, other embodiments are also feasible. For example, the oral treatment device 10 may be an oral irrigator as schematically depicted in FIG. 6, e.g. an air floss device or a water jet device. Such an oral irrigator may comprise a base unit 20 and a handheld unit 30 fluidly connected to the base unit 20 through tubing 25. The base unit 20 may comprise a user interface 22 such as a dial or knob through which a user may select a mode of operation of the oral treatment device 10. The handheld unit comprises a nozzle arrangement 40 through which a fluid stream may be aimed at an interdental region such as a subgingival region to be cleaned by the user. The handheld unit 30 may comprise a switch 32 for enabling/disabling such a fluid stream. In alternative embodiments, the base unit 20 may be omitted as a separate entity and its functionality may be integrated in the handheld unit 30. The first electrode 12 and the sacrificial second electrode 14 may be arranged proximal to the nozzle arrangement orifice 42, with the first electrode 12 typically extending further away from the nozzle arrangement than the second electrode 14 such that the first electrode 12 can contact an ACP formulation separately applied to the teeth of a user proximal to the user's tooth whilst the second electrode 14 is also arranged to contact the ACP formulation but at a greater distance from the user's tooth than the first electrode 14. The oral irrigator may have a dedicated mode of operation in which the fluid stream is disabled but the provision of the potential difference across the first electrode 12 and the second electrode 14 is enabled such as to stimulate precipitation of calcium phosphate from the ACP formulation as previously explained without disturbing the applied ACP formulation by generation of a fluid stream.

[0050] The oral treatment device 10 may also take the form of an electric toothbrush, e.g. a sonic toothbrush, as schematically depicted in FIG. 7. In this embodiment, the first electrode 12 and the sacrificial second electrode 14 may be positioned in the (detachable) brush head 35 of the electric toothbrush, with the (rechargeable) power source 50 being located in the base of the electric toothbrush. For example, the first electrode 12 may be located in amongst the brush hairs 37 of the brush head 35, whereas the second electrode 14 may be located at the interface between the brush hairs 37 and the brush head 35 such that the first electrode 12 can contact an ACP formulation separately applied to the teeth of a user proximal to the user's tooth whilst the second electrode 14 is also arranged to contact the ACP formulation but at a greater distance from the user's tooth than the first electrode 14. The electric toothbrush may have a dedicated mode of operation in which the brush head is disabled but the provision of the potential difference across the first electrode 12 and the second electrode 14 is enabled such as to stimulate precipitation of calcium phosphate from the ACP formulation as previously explained without disturbing the applied ACP formulation by brushing movements.

[0051] An ACP formulation activation kit may be provided by combining the oral treatment device 10 according to any of the herein described embodiments with an ACP formulation, e.g. a CPP-ACP formulation or any other suitable ACP formulation. The ACP formulation preferably is a single-phase composition comprising both the calcium source, e.g. CaCl.sub.2, and the phosphate source, e.g. NaH.sub.2PO.sub.4. For example, an equimolar mixture of CaCl.sub.2 and NaH.sub.2PO.sub.4 yields a formulation having a pH of around 4.2 whereas NaH.sub.2PO.sub.4 can be mixed Na.sub.2HPO.sub.4 with to increase the pH of the formulation, which may be desirable as a formulation that is too acidic can cause enamel erosion. It was found that by mixing NaH.sub.2PO.sub.4 with Na.sub.2HPO.sub.4 the pH of the formulation could be increased to 5.5 without significant calcium phosphate precipitation occurring in the formulation. The pH of the single phase formulation may be in a range of 4-6 and preferably is in a range of 4.5-5.5 to prevent significant calcium phosphate precipitation in the formulation whilst preventing the formulation from becoming overly acidic, which may be detrimental to the teeth to which the formulation is applied, especially when the formulation is left in situ for a period of time prior to activation of the electrochemical reaction with the oral treatment device 10 causing the pH local to the teeth to increase to around 8.5 by the formation of hydroxide ions at the first electrode 12 as previously explained. Of course, other phosphate salts, e.g. potassium salts, and other calcium salts, e.g. nitrate salts may be used in the ACP formulation. In addition, fluorides, thickeners, scaffold formers such as peptides, preservatives, taste components and so on may be added to the ACP formulation. In a particularly advantageous embodiment, the ACP formulation comprises KNO.sub.3, which increases the electrical conductivity of the ACP formulation and reduces nerve sensitivity of (sensitive) teeth.

[0052] FIG. 8 is a flowchart of a method 100 according to embodiment of the present invention. The method 100 starts in operation 101 with the provision of an ACP formulation and an oral treatment device 10 according to any of the herein described embodiments, e.g. in the form of a kit of parts, or separately. In operation 103, the ACP formulation is applied to the one or more teeth to be remineralized, e.g. with the oral treatment device 10 in case the oral treatment device 10 is an applicator such as a dental tray, or separately. The method 100 preferably further comprises optional operation 105, in which the calcium, phosphate and, if present, fluoride ions of the applied ACP formulation are allowed to transport into the porous tooth structure, e.g. by diffusion or by means of active ion transport such as through iontophoresis.

[0053] Next, in operation 107, the applied amorphous calcium phosphate formulation is contacted by the first electrode 12 proximal to the tooth to be treated and by the sacrificial second electrode 14 of the oral treatment device 10, after which the method 100 proceeds to operation 109 in which a potential difference is applied across the first electrode 12 and the sacrificial second electrode 14 of the oral treatment device 10 causing an increase in pH at the first electrode 12 though the formation of hydroxide anions and the formation of cations of the sacrificial material at the second electrode 14. The local increase of the pH at the first electrode 12 in close proximity to the tooth to be treated stimulates the precipitation of calcium phosphate in the pores and on the surface of the tooth, thereby remineralizing the tooth. Upon termination of the applied potential difference, the method 100 terminates in operation 111.

[0054] In order to demonstrate proof of concept, an experiment was conducted in which a commercially available ACP formulation was deposited on three sintered porous polyamide-12 tiles mimicking a porous tooth surface as shown in FIG. 9. A fourth sintered porous polyamide-12 tile (top right corner) was left uncovered as a negative control. In the experiment, the ACP formulation on the tile in the top left corner was used as a positive control, the ACP formulation on the tile in the bottom left corner was used as per the directions provided with the commercially available ACP formulation and the ACP formulation in the bottom left corner was contacted with a Pt electrode (cathode) and a Zn electrode (anode) across which a voltage of 1.5V was applied corresponding to a current of approximately 6 mA, causing immediate bubbling at the Pt electrode and white precipitation on the tile. The results after 30 minutes are shown in FIG. 10, which clearly shows a significant increase in calcium phosphate precipitation on the bottom right tile exposed to the electrochemical reaction compared to the bottom left tile for which the directions of use of the ACP formulation were followed and the top left tile (positive control tile).

[0055] After 30 minutes, the gels were rinsed off the bottom left and bottom right tiles using slowly running tap water to mimic a user drinking, and wiped with a tissue to mimic the action of the user's tongue. The results are shown in FIG. 11. Whilst the bottom left tile showed no visible deposits, the bottom right tile clearly visible deposits can be observed, thereby demonstrating that the exposure of the ACP formulation to the electrochemical reaction significantly enhances calcium phosphate deposition compared to the directed use of the ACP formulation. The positive control tile (top left corner) was simply dried over 1 week, thereby showing the maximum possible deposition from the ACP formulation.

[0056] It should be noted that the above-mentioned embodiments illustrate rather than limit the invention, and that those skilled in the art will be able to design many alternative embodiments without departing from the scope of the appended claims. In the claims, any reference signs placed between parentheses shall not be construed as limiting the claim. The word “comprising” does not exclude the presence of elements or steps other than those listed in a claim. The word “a” or “an” preceding an element does not exclude the presence of a plurality of such elements. Measures are recited in mutually different dependent claims can advantageously be combined.