Dental care product for tooth whitening

Abstract

The present invention relates to the field of dental care, in particular, to a dental care product such as toothpaste (dentifrice), prophylactic paste, tooth powder, tooth polish, tooth gel, chewing gum, candy, lozenge, mouthwash, whitening strip, coated dental floss, coated toothbrush, paint-on gel, varnish, veneer, and tube, syringe or dental tray comprising a gel or paste, mouthwash, whitening strips and trays for whitening teeth, wherein the product comprises mineral particles such as crystals and a compound, preferably, a protein capable of forming a matrix which is a hydrogel, wherein the product comprises a fluorophore. The mineral particles may comprise, e.g., calcium phosphate, preferably, hydroxyapatite, preferably, in crystalline form. The protein matrix may comprise, e.g., a self-assembling peptide. The product also comprises a fluorophore, which may be a fluorescent amino acid residue of the protein matrix. The invention also relates to cosmetic use of the dental care product for whitening teeth or for use in treatment of a sensitive tooth or sensitive teeth and/or in prevention or treatment of caries, as well as a related method for tooth whitening.

Claims

1. A dental care product comprising 0.4-40 wt % calcium phosphate particles and 0.001-5 wt % of a self-assembled protein forming a hydrogel, wherein the particles have a size of 0.01-50 m, wherein the self-assembled protein comprises the amino acid sequence SEQ ID NO: 1.

2. The dental care product of claim 1, wherein said calcium phosphate particles comprise hydroxyapatite.

3. The dental care product of claim 1, wherein the dental care product is selected from the group consisting of toothpaste, prophylactic paste, tooth powder, tooth polish, tooth gel, chewing gum, candy, lozenge, mouthwash, whitening strip, coated dental floss, coated toothbrush, paint-on gel, varnish, veneer, and tube, syringe or dental tray comprising a gel or paste.

4. The dental care product of claim 1, comprising 0.5-40 wt % of said calcium phosphate particles and 0.02-1 wt % of said protein, wherein the dental care product is a toothpaste or gel.

5. The dental care product of claim 1, wherein 30-70% of said calcium phosphate particles have a size of 200-600 nm.

6. The dental care product of claim 1, wherein the product comprises hydrogenated starch hydrolysate, aqua, hydrated silica, PEG-8, cellulose gum, sodium monofluorophosphate, aroma, sodium saccharin, citric acid, sodium hydroxide, dicalcium phosphate, self-assembling peptide having the amino acid sequence SEQ ID NO: 1, calcium glycerophosphate, sodium chloride, sodium sulfate, limonene, cinnamal, CI 42090, and added hydroxyapatite particles.

7. The dental care product of claim 1, wherein said particles have a size of 1-25 m.

8. The dental care product of claim 1, wherein said particles have a size of 4-20 m.

9. The dental care product of claim 4, comprising 0.5-40 wt % of said calcium phosphate particles and 0.05 wt % of said protein, wherein the dental care product is a toothpaste or gel.

10. The dental care product of claim 4, wherein the dental care product is coated on dental floss or a toothbrush.

11. A method for treating a sensitive tooth, prevention or treatment of caries, tooth whitening, or any combination thereof, comprising administering the dental care product of claim 1 to a tooth in need thereof.

12. The method of claim 11, wherein the composition is administered one, two or three times a day on 1, 2, 3, 4, 5, 6, 7 or more days.

Description

LEGENDS

(1) FIG. 1 (A) Electron microscopy picture of tooth surface treated with mixture of P11-4 matrix and hydroxyapatite particle suspension. The surface of the tooth shows tightly bound particles. (B) Electron microscopy picture of tooth surface treated only with hydroxyapatite particle suspension in water. The surface shows unregular positioning of particles on the surface.

(2) FIG. 2 Photographic assessment of the whitening effect of different hydroxyapatite particles on clay plates in the absence (1-4) and presence (1+-4+) of self-assembling peptide (Curodont Protect), according to the protocol of example 2. The pictures show the clay plates after brushing with a tooth brush.

EXAMPLES

Example 1

(3) Materials and Methods

(4) Suspensions of oligopeptide 104 (5 mg/ml) with or without hydroxyapatite particles (average size d50300 nm (Horiba); 40-60% crystallinity, 25 wt %) were generated.

(5) The suspensions were directly applied onto an enamel surface of a tooth, and residues washed off (10 sec). The specimen was stored in distilled water for 24 hours at 37 C. The procedure was repeated 3 times.

(6) The tooth colour was measured with a dental spectrophotometer (VITA Easyshade). The illumination conditions were standardized with a black box as the background for the teeth during the measurement. The tip was applied perpendicular to the tooth surface and the average L*a*b-values from three repetitions were used for evaluations. Colour measurement were done at baseline (t1=without treatment), 24 hours after first application (t1), 24 hours after second application (t3), 24 hours after the third application (t4).

(7) The mean changes of the L*a*b-values between different measurements in each group were expressed as E (according to ISO 28399).

(8) Results

(9) The results are provided in Table 2 below:

(10) TABLE-US-00002 TABLE 2 Test (HA + Control (HA only) oligopeptide 104) E (t2-t1) - 1.sup.st application 2.3 4.6 E (t3-t2) - 2.sup.nd application 1.1 1.9 E (t4-t3) - 3.sup.rd application 1.5 0.6

(11) The experiment shows that, surprisingly, the combination of a protein matrix according to the invention with HA significantly increases the whitening effect seen upon application of HA only.

Example 2

(12) Test Protocol

(13) 1. A ceramic plate made from clay is divided into four compartments using colorless nail polish. All chemicals substances are weighed out and combined in a tube. The tube is filled with nanopure water ad 100% wt. If gelatin is used, the suspension is heated in a water bath by 80 C. during 5 minutes. Afterwards the suspension is mixed by a vortex mixer. The suspension is ready to be applied to the ceramic plate; this is done in two pipet steps by a volume of 50 l. Between the two pipet steps a break of 10 minutes is done. The ceramic plate is dried for about 3 hours. 2. The ceramic plate is incubated in nanopure water for 24 hours. After the incubation, the ceramic plate is removed and left to dry. 3. The whiteness of the ceramic plate is measured by the Vita Easyshade spectrophotometer (Advance 4.0, SN: H26818, Vita Zahnfabrik GmbH, Bad Sackingen). Each field is measured three times and the average value used. 4. The described procedure (1-3) is repeated three times. The mean changes of the L*a*b*-values between different measurements in each group were expressed as E which was calculated using the method according to ISO norm 28399:2011 (Products for external tooth bleaching). 5. After three applications, the ceramic plate is brushed by an ultrasonic toothbrush at a distance of 0.5 cm for 2 minutes. The Lab values of the plate are measured again, as described above.
Tested Materials

(14) Different compositions according to the invention and to the prior art were tested according to the test protocol described above. % relates to wt/wt %. Water is added ad 100%. Curodont Protect comprises 1 mg/g Oligopeptide 104.

(15) TABLE-US-00003 TABLE 3A Compositions comprising different HA particles with or without self-assembling peptide/Curodont Protect Curodont PS Water Protect SAP No. Powder %[wt] [m] %[wt] %[wt] [w/w] 1 -TCP sintered 0.4 20 99.6 CAMCERAM 2 2 -TCP sintered 0.4 20 99.6 CAMCERAM 2 3 50% HA + 50% -TCP 0.4 25/32 99.6 4 40% HA + 60% -TCP 0.4 25/32 99.6 1+ -TCP sintered 0.4 20 92.9 6.7 6.7*10.sup.3 CAMCERAM 2 2+ -TCP sintered 0.4 20 92.9 6.7 6.7*10.sup.3 CAMCERAM 2 3+ 50% HA + 50% -TCP 0.4 25/32 92.9 6.7 6.7*10.sup.3 4+ 40% HA + 60% -TCP 0.4 25/32 92.9 6.7 6.7*10.sup.3

(16) TABLE-US-00004 TABLE 3B Whithening effect of different HA particles with or without self-assembling peptide/Curodont Protect.sup.. E refers to changes to baseline E 24 h E 24 h E 24 h E 24 h after 1. after 2. after 3. after teeth No. Application* Application* Application* brushing* 1 1.8 4.2 3.4 3.0 2 1.0 3.4 2.0 1.7 3 1.8 4.3 3.0 3.0 4 2.1 3.7 2.5 3.5 1+ 4.8 12.3 8.0 7.8 2+ 5.8 11.1 8.1 7.4 3+ 4.6 5.8 7.3 6.6 4+ 3.6 5.2 6.2 6.8 *corrected by baseline

(17) TABLE-US-00005 TABLE 4A Compositions comprising different amounts of HA Curodont PS TWEEN Protect Glycerol Gelatin PEG No. Powder %[wt] [m] %[wt] %[wt] %[wt] %[wt] %[wt] NF1** HA raw 0.5 <10 0.1 2 27 0.5 30 calcined 900 C./3 h NF2** HA raw 1 <10 0.1 2 27 0.5 30 calcined 900 C./3 h NF3** HA raw 2 <10 0.1 2 27 0.5 30 calcined 900 C./3 h

(18) TABLE-US-00006 TABLE 4B Whithening effect of compositions comprising different amounts of HA E 24 h E 24 h E 24 h E 24 h after 1. after 2. after 3. after teeth No. Application* Application* Application* brushing* NF1 1.5 5.8 5.8 4.4 NF2 1.8 7.8 8.6 6.6 NF3 4.0 7.8 7.8 7.6 *corrected by baseline

(19) The experiment demonstrates that different amounts of HA, together with self-assembling peptide, have a whitening effect, which is improved with a higher amount of HA.

(20) TABLE-US-00007 TABLE 5A Comparative compositions from the prior art; 31JP composition according to example 31 of JP2008/081424 8% lactoferrine, 2% lactoferrine hydrolysate, 43% glycerol, 23.5% polyethylenglycol (PEG), 15% silicic acid anhydride 5% hydroxyapatite 10 m 3% sodium methylcellulose 0.3% sodium lauryl sulfate 10JP composition according to example 10 of JPH115722 (mouth wash) 1% hydroxyapatite 1 m 2% ascorbic acid 1% sodium ascorbate 0.5% collagen 0.5% gelatin/collagen decomposition product 10% glycerol 1% ethanol

(21) TABLE-US-00008 TABLE 5B Whithening effect of compositions according to the prior art E 24 h E 24 h E 24 h E 24 h after 1. after 2. after 3. after teeth No. Application* Application* Application* brushing* 31JP 0.7 3.0 2.3 1.2 10JP 3.3 1.0 2.2 2.5 *corrected by baseline

(22) The comparison with prior art compositions shows that the compositions of the present invention are surprisingly much more suitable for tooth whitening. In particular, it should be noted that after application, composition 31JP built up a thick crust, which, by itself, floated off during the 24 hour incubation in water. Composition 10JP turned to a yellow colour.

Example 3

(23) A mono-centric uncontrolled cosmetic study with 40 volunteers desiring lighter/whiter teeth was carried out. The primary goal of the study was assessment of the whitening effect of the assessed product in vivo, using a dental spectrometer (VITA easyshade). Secondary goals were

(24) a) assessment of safety and tolerability of the product,

(25) b) identification and verification of application frequency of the product,

(26) c) assessment of the durability of the whitening effect,

(27) d) assessment of an additional effect of repeated application.

(28) All subjects were between 18 and 75 years old. At least one tooth had to reach a brightness level of >=15 with VITA easyshade. The subjects had healthy incisors and canines of the upper jaw, i.e., free from buccal caries, no erosion, no partial restorations (said criteria applied for the at least one tooth which had to reach the brightness level of >=15 with VITA easyshade). The subjects further had to understand all procedures and be able and willing to follow the instructions, they had to agree to all measurements and controls, and they had to sign a corresponding declaration before the start of the study. Subjects with general sensibility to sugar, bad oral hygiene, fluorosis on the studied teeth, or subjects who took part in another clinical study or performed bleaching during the study were excluded.

(29) The tested product consisted of 50% Curodont Protect (comprising 1 mg Oligopeptide 104/g Curodont Protect, accordingly, the product contained 0.5 mg/g Oligopeptide 104, i.e., 0.05% of the self-assembling peptide), 25% hydroxyl apatite (d50300 nm (Horiba)) and 25% water).

(30) On day 0, at a dental surgery, the dentist or a member of the study team applied the product to the teeth with a dental tray for upper and lower jaw, respectively. After 5-10 min, the subject spit out the product and flushed his/her teeth with water. On days 1-7, once daily, in the evening after regular toothcare, the subject brushed the frontal teeth for 1-2 minutes with the product. During the time of the study, the subjects were instructed to clean their teeth 2-3 times daily, as usual, using a fluoridated toothpaste, Candida Fresh, and a electric toothbrush (Sonicare).

(31) Brightness of the at least one assessed tooth was recorded with the dental spectrometer before and after the first treatment (D0T), on day 1 (before contact with the product on that day) on day 7 (D7) (before contact with the product on that day) and on day 30 (D30). The mean changes of the L*a*b-values between different measurements in each group were expressed as E (according to ISO 28399). Results are shown in Table 3 below.

(32) TABLE-US-00009 TABLE 6 In vivo effects of tooth whitening according to the invention. The table provides E values in reference to the measurement before treatment, i.e., all values are corrected by baseline. Subject D 0T D 1 D 7 D 30 1 1.52 6.64 2.68 6.71 2 1.21 2.08 4.41 4.01 3 2.08 4.88 5.49 6.24 4 2.25 5.14 5.36 3.90 5 2.16 2.32 2.92 6.36 6 2.05 1.86 5.70 5.17 7 2.30 2.66 3.17 5.17 8 1.87 5.25 7.13 5.51 9 3.11 3.21 6.57 4.84 10 1.59 2.02 4.37 4.88 11 3.48 2.95 4.24 3.44 12 1.41 1.36 5.39 1.38 13 2.40 9.91 2.91 2.54 14 1.09 2.84 2.89 2.75 15 1.46 3.04 2.81 2.54 16 2.52 2.22 2.45 2.28 17 3.23 1.96 2.08 1.81 18 3.56 2.20 4.77 3.16 19 1.45 2.52 1.85 1.63 20 1.42 2.09 1.26 1.76 21 2.33 1.13 2.88 6.75 22 2.90 6.07 2.46 5.70 23 2.60 6.74 1.83 7.18 24 3.50 3.52 4.43 3.31 25 3.18 4.00 3.83 4.79 26 3.57 4.09 5.45 5.10 27 5.94 2.99 3.92 ** 28 3.55 2.60 3.05 3.81 29 4.50 4.68 4.23 3.19 30 3.77 3.00 5.61 1.92 31 3.10 2.49 6.69 2.87 32 3.75 1.98 6.85 2.37 33 1.77 2.73 4.63 3.72 34 3.04 2.93 5.00 2.75 35 2.79 2.96 3.90 2.72 36 3.04 2.16 4.20 2.93 37 2.65 3.59 3.52 3.04 38 1.94 4.40 4.03 5.60 39 1.69 1.69 4.22 5.28 40 2.67 1.85 1.94 2.25 Mean 2.61 3.32 4.03 3.88 ** drop out, therefore no data available

(33) The study clearly shows that significant whitening in tooth colour was obtained by the product of the invention. Already after the first application, visual tooth whitening (E>3) occurred for a lot of the patients. On average, a visual whitening effect was seen after D1. Further improvement occurred after a week of daily treatment at home. Of note, the whitening effect of treatment occurred for all patients, with varying degree. Even after 30 days, the whitening effect was still detectable for most subjects.

(34) Of note, most patients did not have homogenous discolorations or yellowing of teeth. The effects of the composition of the invention on single teeth with previous darker colour were more pronounced than the effects seen in the mean values.

(35) The mean degree of tooth whitening is comparable to state of the art chemical bleaching methods (e.g., leading to E of E of less than 4 for home bleaching, E of about 2.4-5.7 after 7 days, or 2.9-5.5 after 14 days for whitening strips, and up to E 12 for power bleachings (in-office use only) (Gerlach et al., 2002; Demarco et al., 2009; Delfino et al., 2009.)

(36) However, the dental care product and method of the invention has significant advantages over chemical bleaching with regard to undesired effects such as tooth erosion, increased tooth sensitivity etc.

LITERATURE

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