ORAL COMPOSITIONS

Abstract

A chewable composition for teeth-whitening comprising a first region and a second region separated by a barrier layer; the first region comprising carbamide peroxide having water content of about 2% or less, a wetting agent (e.g., glycerin), an anhydrous chewing gum base having water content of about 1% or less, an anhydrous fruit acid, and one or more gum additives; and the second region comprising a chewable composition comprising a gum base, a source of bicarbonate ion, and one or more gum additives. A kit comprising separate chewable compositions corresponding to the first and second regions, and methods for whitening teeth using the chewable composition are also provided.

Claims

1-51. (canceled)

52. A method for whitening teeth in a human subject in need thereof, the method comprising: placing in the oral cavity of the subject a first composition and a second composition; and chewing together the first and second composition; wherein the first composition is a chewable composition comprising, an anhydrous chewing gum base having water content of about 1% or less, an anhydrous fruit acid, carbamide peroxide having water content of about 2% or less, and one or more gum additives, wherein the ratio of gum base: carbamide peroxide: fruit acid, in percent weight relative to the composition, is about 10-50:1-20:0.5-8, and the one or more gum additives are present in an amount sufficient to reach 100% of the weight of the composition; and the second composition is a chewable composition comprising a source of bicarbonate ion, a gum base, and one or more gum additives, wherein the source of bicarbonate ion and the gum base are present, respectively, in a ratio of about 5-30:15-50 in percent weight relative to the second composition, and the one or more gum additives are present at an amount necessary to reach 100% of the weight of the second region, and wherein the total weight of the first and the second composition is about 1 g to about 10 g and the chewing provides about 20 mg to about 400 mg hydrogen peroxide equivalents.

53. The method of claim 52, wherein the source of bicarbonate ion is sodium bicarbonate.

54. The method of claim 53, wherein in the first and the second chewable composition combined, the ratio of fruit acid: carbamide peroxide: sodium bicarbonate, by mass is about 0.5-5:5-20:10-35.

55. The method of claim 52, wherein the second composition further comprises a metal carbonate at about 0.001-1% of the weight of the second composition.

56. The method of claim 52, wherein the fruit acid is citric acid.

57. The method of claim 53, wherein, sodium bicarbonate is present at three times or more the amount of the fruit acid.

58. The method of claim 52, wherein pH of the saliva of the human during chewing is about 5.5 to about 7.

59. The method of claim 52, wherein the composition is chewed for 1 to 30 minutes during the chewing step.

Description

EXAMPLES

Example 1. Discovery of Stability of Chewable Composition Comprising Carbamide Peroxide using Fruit Acid as a Stabilizing Agent

[0152] Sixteen different chewable compositions having different amounts of citric acid and carbamide peroxide were tested for stability. Combinations containing four different levels of citric acid (0%, 1%, 2%, and 5% relative to the weight of the composition), each combined with one of four different levels of carbamide peroxide (1.5%, 5.0%, 10.0%, 15.0% relative to the weight of the composition) were prepared. See Table 1 below, compositions A-P.

TABLE-US-00001 Ingredient Amount Carbamide peroxide variable (mg) Gum base 900 mg Xylitol variable (mg) Spearmint oil (spray-dried)  20 mg Sucralose  30 mg Glycerin  50 mg Citric Acid variable (mg) Silica  40 mg

TABLE-US-00002 TABLE 1 Chewable compositions (2.0 g) having different concentrations of citric acid and carbamide peroxide Citric Acid Peroxide gum (anhydrous) 1.5% peroxide 5% peroxide 10% peroxide 15% peroxide 1% A D G J 2% B E H K 5% C F I L 0% M N O P

[0153] Other than the citric acid and the carbamide peroxide, each composition had the same composition. Any mass change due to change in mass of either citric acid or carbamide peroxide was compensated by the addition of xylitol. Stability was assessed by direct titration of hydrogen peroxide (starch iodide method), and also by pH, as well as by subjective measurements of taste and visual characteristics. The samples were stored as packets sealed under argon in a temperature and humidity-controlled environment of 35° C. and 60% humidity. The results of stability assessment are shown in Table 2 below.

TABLE-US-00003 TABLE 2 Stability of peroxide gum as a function of citric acid concentration Citric Acid- % H.sub.2O.sub.2 Peroxide gum 0 30 90 180 360 combination (days) (days) (days) (days) (days) A 0.5 0.4 0.3 0.2 0.2 B 0.5 0.5 0.5 0.5 0.4 C 0.5 0.5 0.5 0.5 0.4 D 1.6 1.4 1.2 1 0.9 E 1.6 1.6 1.6 1.5 1.4 F 1.6 1.6 1.6 1.6 1.5 G 3.3 2.9 2.8 2.7 2.5 H 3.3 3.3 3.2 3.1 3.1 I 3.3 3.3 3.2 3.2 3.1 J 5.2 4.9 4.5 4.4 3.2 K 5.2 5.1 5.1 5 4.9 L 5.2 5.1 5.1 5 5 M 0.5 0.3 0.2 0 0 N 1.6 1.1 0.6 0.1 0 O 3.3 2.4 1.8 0.9 0.1 P 5.2 4.1 2.1 0.9 0.3

[0154] The results show conclusively that of the sixteen combinations, eight, namely, B, C, E, F, H, I, K, and L demonstrated appreciable stability, i.e., demonstrated shelf life suitable for commercialization. Notably, each of these eight chewable gum composition compositions has citric acid >or =2%,

Example 2. Stable Carbamide Peroxide Gum Prepared by Tablet Press Technology

[0155]

TABLE-US-00004 Ingredient Amount Carbamide peroxide 250 mg Gum base 900 mg Xylitol 850 mg Sorbitol 500 mg Peppermint oil (spray-dried)  25 mg Sucralose  30 mg Citric Acid  50 mg Magnesium Stearate  75 mg Stearic Acid 100 mg Microcrystalline Cellulose 125 mg

[0156] The above-listed ingredients were combined and blended in a ribbon blender at slow speed until homogeneous, then submitted immediately to a tablet press. Circular tablets were ejected at about 2.6 grams per composition.

Example 3. Stable Carbamide Peroxide Chewable Gum Composition Prepared by Extrusion

[0157] The ingredients listed below, in the amounts shown, were used to produce chewable gum compositions by extrusion.

TABLE-US-00005 Ingredient Amount Carbamide peroxide 330 mg Gum base (“PIB/NOVA-T”) 900 mg Xylitol 700 mg Spearmint oil (spray-dried)  20 mg Sucralose  30 mg Citric Acid  50 mg Glycerin  60 mg Silica  40 mg

Example 4. Two Gum Composition Formulations for Maximum Teeth-Whitening

[0158] Thirty-two different combinations of carbamide peroxide containing chewable compositions, namely (“peroxide gum”), B, C, E, F, H, I, K, and L (see Example 1) and sodium bicarbonate containing chewable compositions (“bicarbonate gum”) having the formulation shown below were tested for teeth-whitening efficacy.

[0159] Peroxide containing gum (made by extrusion)

TABLE-US-00006 Ingredient Amount Carbamide peroxide variable (mg) Gum base(“PIB-T/NOVA-T”) 700 mg Xylitol variable (mg) Spearmint oil (spray-dried)  20 mg Sucralose  30 mg Glycerin  50 mg Citric Add variable (mg) Silica  50 mg

[0160] Procedure [0161] 1) Gum base and xylitol were added to a warm mixer and mixing started. [0162] 2) Upon softening of the resulting mixture, about half of the remaining xylitol was added and mixing continued for 2 minutes. [0163] 3) Citric acid, silicon dioxide, and carbamide peroxide were added and mixing continued for approximately 2 minutes. [0164] 4) Glycerin and coolant were added and mixing continued for approximately 1.5 minutes. [0165] 5) Remaining xylitol was gradually added and mixing continued for approximately 2 minutes. [0166] 6) Sucralose was added and mixing continued for approximately for 1 minute. [0167] 7) Flavor was added and mixing continued for 2-3 minutes until batch was uniform. Upon cooling, rectangular pieces, 2.0-2.2g/piece, were extruded.
Bicarbonate Containing Gum (made by Extrusion)

TABLE-US-00007 Ingredient Amount Sodium bicarbonate variable (mg) Amorphous silica  20 mg Gum base (“PIB/NOVA-T”) ( 710 mg Spray dried peppermint oil 100 mg Maltitol syrup 250 mg Xylitol variable (mg) Calcium carbonate  5 mg Sodium carbonate  5 mg Glycerol  20 mg Coating (xylitol) 325 mg Lecithin  2 mg Titanium dioxide  5 mg * Xylitol was added in place of sodium bicarbonate, to achieve appropriate equal masses of the “bicarbonate” chewable gum composition

[0168] Procedure [0169] 1) Gum base, xylitol, and titanium dioxide were added to a warm mixer and mixing started. [0170] 2) Upon softening of the resulting mixture, about half of the remaining xylitol was added and mixing continued for 2 minutes. [0171] 3) Coolant, sucralose, and sodium bicarbonate/silicon dioxide were added to the mixture and mixing continued for about 2 minutes. [0172] 4) Glycerin and remaining half of the maltitol syrup was added and mixing continued for about 1.5 minutes. [0173] 5) Remaining xylitol was gradually added and mixing continued for approximately 2 minutes. [0174] 6) Flavor was added and mixing continued for 2-3 minutes until batch was uniform. Upon cooling, rectangular pieces, 2.0-2.2g/piece, were extruded.

[0175] Subjects chosen for the study had appreciably stained teeth (Vita Shade Guide, Omsk., values >7, i.e., “darker” than “B4”) and had not had teeth-whitening procedure performed for at least 3 years prior. The results, shown below in Table 3, conclusively showed that that six of the thirty two combinations demonstrated appreciable teeth-whitening.

TABLE-US-00008 TABLE 3 Teeth-whitening obtained using various carbamide peroxide bicarbonate gum compositions Peroxide containing gum % BC B C E F H I K L 5 0-1 0-1 0-1   0-1     1-1.5   1-1.5 1.5-2   1.5-2   10 0-1 0-1 0-1   0-1   1.5-2   1.5-2     2-2.5   2-2.5 15 0-1 0-1 1-1.5 1-1.5 3.5-5   2.5-3     3-3.5   3-3.5 0 0-1 0-1 0-1   0-1   0.5-1     1-1.5 1.0-1.5 1.0-1.5 % BC: % sodium bicarbonate in the bicarbonate containing gum

[0176] Compositions made with 15% sodium bicarbonate containing gum performed the best. More specifically, the best combination for teeth-whitening commercial product was found to be the combination of carbamide peroxide gum composition “H” with 15% bicarbonate containing gum composition as its complement. Without being limited by any theory or mechanism of action, it is believed that the most likely reason the “peroxide” gum composition “I” did not perform as well as the composition “H” is that with 5 % citric acid, “I” has excess citric acid that reacts with the bicarbonate ion to reduce the effective amount of bicarbonate, leading to the pH of the oral cavity not being the most favorable to activate the peroxide moiety in-situ. See Table 1. Note that the composition “H” has 2% citric acid.

[0177] Also, some of the test subjects experienced slight discomfort when using the peroxide gum tablets having 15% carbamide peroxide (K, L), whereas no sensitivity was reported with the use of the 10% peroxide gums (H, I) when employed with its 15% bicarbonate gum complement. Notably, it was generally observed that the higher the amount of sodium bicarbonate with respect to the amount of carbamide peroxide, the lower was the observed tooth sensitivity.

Example 5. Two-Gum (Biphasic) Composition made by Extrusion

[0178] The compositions of the peroxide gum and the bicarbonate gum of an exemplary two-gum (biphasic) composition is shown below.

Peroxide Gum

[0179]

TABLE-US-00009 Ingredient Amount Carbamide peroxide 200 mg Gum base 660 mg Xylitol 900 Spearmint oil (spray-dried) 100 mg Glycerin  40 mg Citric Acid  50 mg Sucralose  15 mg Amorphous silica  50 mg

[0180] Procedure [0181] 1) Gum base and xylitol were added to a warm mixer and mixing started. [0182] 2) Upon softening of the resulting mixture, about half of the remaining xylitol was added and mixing continued for 2 minutes. [0183] 3) Citric acid, silicon dioxide, and carbamide peroxide were added and mixing continued for approximately 2 minutes. [0184] 4) Glycerin and coolant were added and mixing continued for approximately 1.5 minutes. [0185] 5) Remaining xylitol was gradually added and mixing continued for approximately 2 minutes. [0186] 6) Sucralose was added and mixed for approximately 1 minute. [0187] 7) SD flavor was added and mixing continued for 2-3 minutes until batch was uniform. Upon cooling, rectangular pieces, 2.0-2.2g/piece, were extruded.

Bicarbonate Gum

[0188]

TABLE-US-00010 Ingredient Amount Sodium bicarbonate 300 mg Amorphous silica  30 mg Gum base (“Nova-T/PIB-T”) 650 mg Spray dried peppermint oil 100 mg Glycerin  60 mg Xylitol 890 mg Surfactant (SLS)  5 mg Calcium carbonate  5 mg Sodium carbonate  5 mg Sucralose  60 mg Titanium Dioxide  5 mg Lecithin  3 mg

[0189] Procedure [0190] 1) Gum base, xylitol, and titanium dioxide were added to a warm mixer and mixing started. [0191] 2) Upon softening of the resulting mixture, about half of the remaining xylitol was added and mixing continued for 2 minutes. [0192] 3) Coolant, sucralose, and sodium bicarbonate/silicon dioxide were added to the mixture and mixing continued for approximately 2 minutes. [0193] 4) Glycerin was added and mixing continued for approximately 1.5 minutes. [0194] 5) Remaining xylitol was gradually added and mixing continued for approximately 2 minutes. [0195] 6) Flavor was added and mixing continued for 2-3 minutes until batch was uniform. Upon cooling, rectangular pieces, 2.0-2.2g/piece, were extruded.

Example 6. Demonstration of Synergistic Teeth-Whitening Activity with Simultaneous use of the Peroxide Gum and the Bicarbonate Gum

[0196] Improvement in teeth-whitening by biphsic gum (combination of peroxide gum and bicarbonate gum) was compared to the improvement in teeth-whitening achieved with the peroxide gun and the bicarbonate gum alone.

[0197] Twelve subjects were chosen, none ever having had their teeth bleached. Their teeth were heavily stained due to smoking. Subjects qualified for the study if they demonstrated whitening levels darker than “B4” grade using the Vita Shade Guide (Classic). The subjects used: (a) either a single peroxide gum prepared according to Example 4 (ca. 2 gram per piece), or; (b) a single bicarbonate gum prepared according to Example 4 (2 gram per piece), or; (c) the two gums together, chewed simultaneously. The gums were chewed for 30 minutes. The results of the chewing are shown in Table 4 below.

TABLE-US-00011 TABLE 4 Teeth-whitening efficacy of peroxide and bicarbonate gum combined compared to that of peroxide gum or bicarbonate gum Type of Gum Peroxide Bicarbonate Peroxide Gum + Subject Gum Gum Bicarbonate Gum 1 0 0 3 2 0 0 2 3 1 0 4 4 0 0 4 5 1 0 5 6 0 0 2 7 0 0 3 8 1 0 4 9 1 1 4 10 1 0 3 11 1 1 5 12 1 1 4 Average 0.58 0.25 3.58 shade change in whitening

[0198] The results show a dramatic increase in whitening observed for the peroxide guru due to the presence of the bicarbonate gum. A tenfold increase in whitening (1000% increase) was observed. Specifically, average whitening levels were observed to be very little (0.58 shade) if any, when the subject only used the “peroxide gum” (no “bicarbonate guru”). Likewise, when the subjects chewed only the “bicarbonate gum,” no appreciable teeth-whitening took place. In stark contrast, when the two gums were chewed together, a shade change of between 2-5 shades was observed, with an average change of about 3.6 shades.

[0199] These data demonstrate a strong whitening effect when both gums are chewed together. The magnitude of the effect is much greater than would be expected from a teeth-whitener in general, and especially from a teeth-whitening gum. The effect is a result of sodium bicarbonate and carbamide peroxide being present together in an oral mixture. Further, the magnitude of the teeth-whitening effect is much greater than would be expected if sodium bicarbonate functioned solely by activating the peroxide by pH control.

Example 7. Single Composition Multi-Phasic Teeth Whitening Tablet

[0200] The three compositions below were compounded using a standard ribbon blender at low speed and pressed into a single multi-layered tablet, having the middle layer (of the three-layer tablet) as the barrier layer comprising anhydrous chewing gum base and no active.

Bicarbonate Layer (Phase)

[0201]

TABLE-US-00012 Ingredient Amount Sodium Bicarbonate 375 mg Amorphous Silica  20 mg Gum base 800 mg Spray dried peppermint oil 100 mg Xylitol 700 mg Calcium carbonate  5 mg Sodium carbonate  5 mg Magnesium Stearate  80 mg Stearic Acid 125 mg Microcrystalline Cellulose 200 mg Coating (xylitol)  25 mg

Peroxide Layer (Phase)

[0202]

TABLE-US-00013 Ingredient Amount Carbamide peroxide 250 mg Gum base 900 mg Xylitol 850 mg Sorbitol 500 mg Peppermint oil (spray-dried)  25 mg Sucralose  30 mg Citric Acid  50 mg Magnesium Stearate  75 mg Stearic Acid 100 mg Microcrystalline Cellulose 125 mg

Intermediary Barrier Layer (Phase)

[0203]

TABLE-US-00014 Ingredient Amount Amorphous silica  20 mg Gum base 800 mg Spray dried peppermint oil 100 mg Xylitol 800 mg Sorbitol 225 mg Magnesium Stearate  80 mg Stearic Acid 155 mg Microcrystalline Cellulose 300 mg

Example 8, Evidence of Chemotherapeutic Effect with Simultaneous use of the Peroxide Gum and the Bicarbonate Gum

[0204] All of the test subjects of Example 6 described a lessening of sensitivity to peroxide when the bicarbonate gums having greater than 10% sodium bicarbonate were chewed together with the peroxide gums. This effect was especially noticeable for the peroxide gums comprising 15% carbamide peroxide. In these gums sodium bicarbonate was present between 250 mg and 400 mg and carbamide peroxide was present between 175 mg and 400 mg. Condition of the gums and breath were observed to have improved, especially for those cases where the patients had inflamed gums at baseline (symptoms typical for gingivitis). The counts of anaerobic and aerobic bacteria decreased dramatically, even after only one 30-minute treatment. These results strongly suggest that the two-composition oral treatment helps remediate symptoms of periodontal diseases, and oral malodor, not only by removing stains and debris from the teeth surface, but also by affecting positive change to the micro-flora inherent to the human oral cavity.