Dental Composition

Abstract

The present invention provides dental compositions and devices comprising a rechargeable fluoride delivery system wherein the rechargeable fluoride delivery system comprises a layered double hydroxide with the formula M(II).sub.1-x M(III).sub.x (OH).sub.2(A.sup.n).sub.x/nyH.sub.2O where M(II) is a divalent cation, M(III) is a trivalent cation, A is an anion with a charge, x is a value between 0.2 and 0.33, y is an integer between 1 and 10 and n has a value of 1.

Claims

1. A method of treating or preventing caries, the method comprising applying to a patient in need thereof a dental composition comprising a rechargeable fluoride delivery system, wherein the rechargeable fluoride delivery system comprises a layered double hydroxide with the formula:
M(II).sub.1-xM(III).sub.x(OH).sub.2(A.sup.n).sub.x/nyH.sub.2O where, M(II) is a divalent cation; M(III) is a trivalent cation; A is a chloride anion; the ratio of 1-x to x is between 0.5 and 2.0; y is an integer between 1 and 10; and n has a value of 1.

2. The method according to claim 1 wherein M(II) is selected from the group consisting of Zn, Mg, Ca, Ni and Cu.

3. The method according to claim 1 wherein M(III) is selected from the group consisting of Al, Ga and Fe.

4. (canceled)

5. The method according to any claim 1 wherein the composition is a dental filling material, crown and bridge material, veneer material, an inlay or an onlay, a pit and fissure sealant or a bonding agent or an adhesive.

6. The method according to claim 1 wherein the composition is a toothpaste.

7. The method according to claim 1 wherein the composition is a fluoride varnish, a dental cement, a dental resin or a composite.

8. A dental device incorporating a composition comprising a rechargeable fluoride delivery system wherein the rechargeable fluoride delivery system comprises a layered double hydroxide with the formula:
M(II).sub.1-xM(III).sub.x(OH).sub.2(A.sup.n).sub.x/nyH.sub.2O.

9. A dental device according to claim 8 wherein M(II) is selected from the group consisting of Zn, Mg, Ca, Ni and Cu.

10. A dental device according to claim 8 wherein M(III) is selected from the group consisting of Al, Ga and Fe.

11. A dental device according to claim 8 wherein the device is a denture, orthodontic bracket, orthodontic retainer, splint, crown or bridge.

12-13. (canceled)

Description

[0048] The invention will now be described by way of illustration with reference to the following Examples and figures in which:

[0049] FIG. 1 shows powder X-ray diffraction patterns for LDH, CSLDH and cellulose

[0050] FIG. 2 shows the adsorption isotherms of fluoride on LDH, CSLDH and cellulose at 25 C.

[0051] FIG. 3 shows the adsorption isotherm of fluoride on LDH at 25 C.

[0052] FIG. 4 shows the .sup.19F Magic Angle Spinning (MAS) NMR of NaF treated LDH

[0053] FIG. 5 shows the release of fluoride upon placing NaF treated polymeric discs in deionised water

[0054] FIG. 6 shows the release of fluoride from control and PEM/THFM containing LDH samples (n=5)

[0055] FIG. 7 shows the release of fluoride from PMMA samples containing preloaded LDH with fluoride against time (n=4)

[0056] FIG. 8 shows the comparison of release of fluoride from LDH-containing PMMA samples and LDH-containing PEM samples after initial charging (n=5)

[0057] FIG. 9 shows the cumulative release of fluoride from control PEM discs (time in hours)

[0058] FIG. 10 shows the comparison between average amounts of fluoride released in ppm from samples with LDH powder preloaded with fluoride.

[0059] The following Examples are intended to illustrate the invention and are not to be construed as limiting the invention:

EXAMPLES

Example 1: Synthesis of LDH

[0060] Methods described by Mandal and Mayadevi (Chemosphere 72 (2008) 995-998) were followed.

[0061] Briefly, 0.852 g Zinc Chloride (ZnCl.sub.2) and 0.8335 g aluminium chloride (AICIs) were added to 25 cm.sup.3 of deionised HaO to make a 0.5M solution. This ZnCl.sub.2AlCl.sub.3 salt solution was titrated simultaneously with 2M NaOH from 2 burettes into a beaker containing 25 cm.sup.3 of deionised water. The flow rate of NaOH into the beaker was adjusted to ensure that a pH of 101 was maintained throughout, and was measured continuously with a pH electrode. The solution was stirred continuously. The final solution was left to age for 24 h, after which the solution was topped up to 100 cm.sup.3 by adding deionised H.sub.2O and divided into 4 universal tubes containing 25 mls each. These samples were centrifuged for 3 min at 3000 rpm. The supernatant was pipetted off and pH checked with litmus paper, before rinsing the pellet and re-suspending it in 25 cm.sup.3 deionised H.sub.2O and centrifuging again. This was repeated until the supernatant became neutral to litmus. The solids were left in the universal tubes for 36 h at 80 C. to ensure they were completely dehydrated. Samples were removed from the oven and ground to a fine powder.

[0062] This same procedure was repeated to make a cellulose supported layered double hydroxide (CSLDH) as described by Mandal and Mayadevi. The CSLDH samples were produced by taking 3.371 g cellulose powder which was soaked in 50 cm.sup.3 deionised H.sub.2O for 30 min at 37 C., after which the salt solution as described above and NaOH was titrated into the beaker containing the suspended cellulose solution. The solution was stirred continuously. The LDH and CSLDH were characterised using powder X-ray diffraction (XRD). The diffraction pattern relating to these materials are shown in FIG. 1.

[0063] Powder XRD pattern serves as a structural fingerprint of a given material. The diffraction pattern of pure cellulose matched previous studies. The large peak at 11.4, which is absent n cellulose, corresponds to the interlayer spacing of Zn/Al-LDH and corresponds with that of previous studies by Mandal and Mayadevi. However, in contrast the remaining peaks within the diffraction pattern for LDH are of a reduced intensity and significantly broader when compared with CSLDH. This indicates that whilst the LDH prepared here has the same chemical composition the crystallite size is smaller. Such an observation is important as smaller crystallites are likely to contribute to faster fluoride uptake and release.

Example 2: Adsorption Isotherm of Fluoride on LDH

[0064] Serial dilutions of 0.01M, 0.0075M, 0.005M, 0.0025M, 0.001M, 0.0005M and 0.00001M were made from a sodium fluoride (NaF) stock solution (0.1 M). A fluoride ion selective electrode was calibrated using these concentrations starting with the highest concentration and leaving the probe in the solution and recording the mV reading at 3 min intervals until 2 consecutive readings within 0.3 mV of were achieved. LDH (0.4 mg) was weighed into 15 ml universal tubes and 10 cm.sup.3 of NaF solution (0.01, 0.005, 0.0025, 0.0020, 0.0015, 0.0010, 0.0005 M) added and the samples agitated at 25 C. for 60 min.

[0065] After 60 min the remaining fluoride in solution was measured with the ion selective electrode for 3 min and then repeatedly at intervals until the reading remained consistent (0.3 mV). This was repeated for each of the three samples measured. The fluoride uptake could be determined from the decrease in fluoride concentration in solution (FIG. 2). Table 1 below shows the adsorption values.

TABLE-US-00001 TABLE 1 Fluoride concentration Cellulose LDH CSLDH Initial Initial Final Adsorption Final Adsorption Adsorption conc. conc. conc. Capacity conc. Capacity Final conc. Capacity (M) (mg/l) (mg/l) (mg/g) (mg/l) (mg/g) (mg/l) (mg/g) 0.0005 0.05 13.81 0.734 1.308 4.922 7.276 0.995 0.001 0.1 20.622 2.183 1.378 10.152 18.655 1.692 0.0015 0.15 31.337 3.234 1.925 15.264 29.61 2.42 0.002 0.2 44.411 4.043 5.271 19.676 45.587 2.784 0.0025 0.25 55.708 5.034 7.188 24.445 57.434 3.447 0.005 0.5 120.495 9.141 80.922 32.254 133.783 5.523 0.01 1 243.07 18.07 220.645 49.809 319.88 7.252

[0066] The equilibrium adsorption capacity (q.sub.e) of the LDH at different initial fluoride concentrations was calculated using the formula:

q.sub.e=(C.sub.0-C.sub.f)V/W100

where C.sub.0: Initial fluoride conc. (mg I.sup.1); C Fluoride conc. after adsorption (mg I.sup.1); V: volume of NaF sol. (ml); W: weight of adsorbent (g). The LDH was found to exhibit a maximal adsorption capacity of 44.7 mg/g when placed in a 100 mM solution of NaF for 1 hour (FIG. 3).

[0067] The fluoride uptake by the LDH was confirmed by performing .sup.19F Magic Angle Spinning NMR (FIG. 4). The .sup.19F spectra revealed two broad resonances as 112.6 and 145.2 ppm. This demonstrates the ability of LDH to take up fluoride as no .sup.19F spectra could be obtained prior to fluoride immersion studies. It also emphasises that fluoride occupies two chemically distinct positions within the layered structure of LDH. The peak at 112.6 ppm probably corresponds to a fluoride bound to zinc, whilst the peak at 145 ppm probably corresponds to a fluoride bound to aluminium. The additional sharp peak at 123.6 ppm is associated with fluoride ions that are non-specifically bound adsorbed on the periphery of the material.

Example 3: Desorption of Fluoride by LDH

[0068] Samples of LDH previously immersed in NaF solutions were centrifuged for 3 min at 3000 rpm, and all supernatant removed. They were then re-suspended in 10 ml deionised H.sub.2O. Fluoride measurements were made using the fluoride ion selective electrode and readings were taken at 3 and 6 min intervals and then samples were left stirring for 1 h before re-measuring the fluoride concentration of the solution. Readings were taken again after 72 h, with the samples being stirred continuously. The results are displayed in Table 2 below. Each of the samples measured highlighted that the LDH material slowly releases the adsorbed fluoride over time.

TABLE-US-00002 TABLE 2 Adsorption t = 0 t = 1 h t = 72 h Initial Conc. (M) Conc. (M) Conc. (M) Conc. (M) 0.0005 8.66E07 6.84E07 2.13E06 0.001 1.54E06 1.78E06 4.21E06 0.0015 1.94E06 2.28E06 6.17E06 0.002 3.33E06 4.17E06 8.94E06 0.0025 6.04E06 6.48E06 1.13E05 0.005 1.48E05 2.79E05 4.15E05 0.01 7.26E06 1.05E05 1.45E05

Example 4: Polymeric Delivery Systems

[0069] Polyethyl methacrylate (PEM) and Tetrahydrofurfuryl methacrylate (THFM) discs were made using 5 g of polyethyl methacrylate (PEM) powder and 3 ml of Tetrahydrofurfuryl methacrylate (THFM) monomer containing 2.5 wt % Dimethyl pars toluidine (DMPT), an amine accelerator. On adding the THFM to the PEM the material formed a gel which polymerised (at room temperature) into a hard, glassy resin. Similarly PEM/THFM & 20% hydroxyethylmethacrylate (HEMA) blanks were made providing a polymeric control with differing hydrophilicity.

[0070] The LDH-containing PEM/THFM discs were prepared by adding the required weight % LDH to the PEM powder.

[0071] Discs were prepared by using 1 mm thick10 mm diameter moulds and by placing the gel between 2 glass plates (covered with acetate sheets as mould release) and then placed under pressure with a bull-dog clip to produce non-porous samples. These were left until set approx. 15 min. This procedure was repeated, incorporating 12 wt % LDH with the polymer powder, mixing the two powders until evenly dispersed. Discs removed from the PTFE moulds were trimmed, edges smoothed with silicon carbide paper and weighed.

[0072] Analogous systems were created in cold cure polymethyl methacrylate (PMMA). Briefly, self-cured (room temperature cured) PMMA polymeric discs were prepared (addition polymerisation reaction) by mixing the polymer powder (PMMA) with the methyl methacrylate monomer liquid (MMA). The powder was kept at room temperature and the liquid monomer was stored in a dark bottle in the refrigerator at 4 C. approximately. PMMA control discs were prepared by adding 5 grams PMMA powder to 2.3 ml MMA liquid. The powder and liquid were mixed and poured in the PTFE mould of the same dimensions as the one used for PEM/THFM.

[0073] Five samples of each polymer PEM/THFM, PEMITHFMILDH. PEM/THFM/HEMA and PEM/THFM/HEMA/LDH as well as PMMA/THFM and PMMA/THFM/LDH were placed in 15 ml universal tubes with 10 ml 0.01 M NaF solution. These were left agitating for 24 h, after which the fluoride concentration in solution was measured and the adsorption capacity calculated as described previously. The polymeric discs were blot dried and weighed to determine the total absorption of H.sub.2O and NaF. When compared with GIC, the polymeric discs showed faster adsorption of fluoride (data not shown).

Example 5: Fluoride Release from Polymeric Systems in De-Ionised Water

[0074] The polymeric discs of each polymer were placed in 5 ml de-ionised HO and the fluoride concentration measured with a fluoride electrode as a function of time over a 10 day period. The polymers containing no LDH (control: PEM/THFM and PEM/THFM/HEMA) gave no fluoride release. In contrast the polymer samples loaded with LDH resulted in significant fluoride release (FIG. 5). The PEM/THFM/LDH polymer gave up to 0.11 mM (2.4 ppm) of fluoride over a 3 day period. (FIG. 6).

[0075] Analogous discs to the ones described above were generated in PMMA containing 5% and 7% wt/wt LDH that had been pre-treated with NaF. These pre-loaded discs were then analysed with respect to their capacity to release fluoride in to a static solution of deionised water. The release was monitored for 120 days identifying a slow-prolonged release of fluoride over this time period (FIG. 7).

Example 6: Fluoride Release from Polymeric Systems in Artificial Saliva

[0076] Artificial saliva was prepared as follows: 800 ml deionized water were added in a beaker with a magnetic stirrer and 15.09 grams of tris powder were added slowly until completely dissolved, 44.2 ml HCl was then added and the mix was poured in a plastic bottle and left in an incubator at 37 C. overnight. The next day the pH of the solution was adjusted to approximately 7.25-7.4 by addition of HCl and the bottle was topped up with deionized water to a volume of two litres.

[0077] PEM/THFM/LDH and PMMA/THFM/LDH discs analogous to those discussed earlier were investigated to evaluate their capacity to release fluoride within an artificial saliva medium. The release of fluoride, over the same conditions as described previously, was analogous to that produced within aqueous medium (FIG. 8). FIG. 9 shows release of fluoride from PEM/THFM/LDH discs when compared to control discs. Average amounts of fluoride released from the LDH containing PMMA and PEM/THFM systems studied are shown in FIG. 10.