Tooth whitening gels, methods and uses comprising modified niobium compounds

Abstract

The present technology relates to products for tooth whitening based on the in situ generation of active oxygen in the form of oxygen free radical species. The whitening gel comprises a modified niobium compound and its activity is primarily maximized when it is applied together with a low concentration of hydrogen peroxide of 1% to 10% (preferably 3% by mass) and stabilized with a thickener (preferably carbopol). The whitening sol can be used for tooth whitening without the need for additional light treatment, which makes it more effective than commercial products when used for tooth whitening and has significant potential to reduce side effects (allergy and inflammation). The developed product showed no cytotoxicity and no significant inflammatory effects were observed in dental pulp tissue. The present technology also describes a method for preparing the whitening gel.

Description

[0001] The present technology relates to products based on the in situ generation of active oxygen in the form of oxygen free radical species for tooth whitening. The whitening gel comprises a modified niobium compound and its activity is primarily maximized when it is applied together with a low concentration of 1% to 10% (preferably 3% by mass) hydrogen peroxide and stabilized with a thickener (preferably carbopol). The whitening gel can be used for teeth whitening without the need for additional light treatment, which makes it more effective than commercial products when used for teeth whitening and has significant potential to reduce side effects (allergy and inflammation). The developed product showed no cytotoxicity and no significant inflammatory effects were observed in dental pulp tissue. The present technology also describes a method for preparing the whitening gel.

[0002] In recent years, the demand for teeth whitening in cosmetic clinics and dental offices has increased significantly. However, in commercial products such as whitening or brightening gels, high concentrations (6% to 35%) of hydrogen peroxide (H2O2) are used in their formulations. Exposure of teeth to peroxides can cause side effects such as sensitivity, damage to the dental pulp, enamel and periodontal tissues. In the prior art, several studies have emphasized the importance of using materials based on inorganic compounds to minimize these adverse effects (Application of Titanium Dioxide Nanotubes to Tooth Whitening, NanoBiomedicine, Volume 6, Issue 2, 12 December 2014, Pages 63-72) (Synthesis of metalion-histidine complex functionalized mesoporous silica nanocatalysts for enhanced light-free tooth bleaching, Acta Biomaterialia, Volume 7, Issue 5, 7 January 2011, Pages 2276-2284).

[0003] In the prior art, several studies can also be found that emphasize the use of niobium compounds for oxidation reactions, including organic pollutants present in industrial effluents (Photocatalytic degradation of hazardous Ponceu-S dye from industrial wastewater using nanosized niobium pentoxide with carbon, Desalination, Volume 269, Issue 1-3, 4 November 2010, Pages 276-283) (Amphiphilic niobium oxyhydroxide as a hybrid catalyst for sulfur removal from fuel in a biphasic system, Applied Catalysis B: Environmental, Volume 147, 6 August 2013, Pages 43-48).

[0004] The use of reactive materials for teeth whitening has been reported in various documents. US Pat. No. 20040180008, entitled "Dental bleaching agent kit and the method for bleaching teeth," from 2004, and US Pat. No. 20060222604, entitled "Method for bleaching teeth and bleaching agent for teeth," from 2002, report the combined use of titanium compounds and visible light based on a photocatalytic reaction. Furthermore, the importance of using peroxides to ensure teeth whitening is emphasized.

[0005] Inventions related to the 1995 patent US5645428 entitled "Method for whitening teeth" reported the effectiveness of teeth whitening using mixtures of different catalysts and peroxides exposed to argon laser radiation and carbon dioxide lasers. The method used other materials including buffers, stabilizers, desensitizers, and thickeners.

[0006] Patent US5032178, entitled "Dental composition system and method for bleaching teeth" from 1990, describes materials from the group consisting of manganese sulfate and iron sulfate, along with other products including hydrogen peroxide, for use in the presence of visible light radiation for tooth whitening.

[0007] Document BR102013027175-6, filed in 2013 and titled “Teeth whitening accelerator,” relates to a mixture of ferric nitrate and copper nitrate together with hydrogen peroxide to promote effective whitening.

[0008] Document BR102014010685-5, filed in 2014 and entitled “Teeth whitening maximizer”, describes natural catalysts such as enzymes of the peroxidase family, such as catalase, with rapid decomposition of hydrogen peroxide or carbamide peroxide and effective teeth whitening.

[0009] Document PI 0801862-6 from 2008 entitled "Teeth whitening gel with micro or nano solid particles that absorb energy and is thermally conductive" relates to conductive inorganic, ceramic or organic micro or nano particles incorporated into a peroxide-based whitening gel which, in addition to providing better efficiency in teeth whitening, also minimizes side effects such as hypersensitivity.

[0010] The use of materials based on niobium compounds (which may be niobium pentoxide, niobic acid, and niobium oxyhydroxide) for tooth whitening proposed in this technology is unprecedented. It emphasizes the unprecedented use of oxalate in the activation of hydrogen peroxide or an organic peroxide, primarily due to the in-situ generation of free radical oxygen species from the reaction of niobium with H₂O₂, and the stabilization of the oxygen species with commercial carbopol. Another novelty of this invention is that the added hydrogen peroxide decomposes by reacting with the niobium species, generating reactive oxygen species, reducing the presence of free peroxides and eliminating sensitivity. In this way, in addition to allowing for low-cost material preparation, allergic side effects during processing can be minimized, which may facilitate its commercialization.

[0011] The oxygen species generated during the decomposition of H2O2 have an oxidative effect capable of breaking the chemical bonds of the molecular chains of chromophore groups (substances that impart color to teeth). The low concentration of peroxide in the presented product (approximately 2% by mass) is sufficient to achieve this effect, thanks to three major technological innovations: (i) the niobium compound acts effectively and rapidly upon activation to generate reactive free radical species; (ii) free peroxide is reduced, reducing sensitivity during bleaching; and (iii) carbopol stabilizes the free radicals, preventing them from decomposing, which enhances tooth whitening.

[0012] In addition, the use of the gel in teeth whitening does not require the use of radiation to decompose the peroxide and does not require significant changes in pH, thereby reducing processing time in the clinic or at home. These features provide great commercial potential for products produced in this technology.

[0013] The present technology involves the development of materials using niobium sources as raw materials to obtain whitening nanoparticles. The use of niobium compounds in the preparation of niobium-containing tooth whitening gels, as proposed in the present technology, has not been reported in the scientific literature and could facilitate another commercial application for this important chemical element, currently used primarily in the metallurgical industry. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 Shown is an application syringe containing a teeth whitening gel.

[0015] Figure 2 The parameters of brightness, color intensity / luminosity and hue obtained using the VITA 3D MASTER sample card are presented using different niobium compounds.

[0016] Figure 3 Shown are photographs of bovine teeth before and after treatment with materials G1 (A) and G3 (B).

[0017] Figure 4 Shown are SEM images of rat teeth whitened with whitening gel G1 (A), commercial G3 (B), and a control group (C) at magnifications of 200X (upper panel) and 500X (lower panel).

[0018] Figure 5 Representative images of sections stained with hematoxylin and eosin are presented, showing the pulp of the tooth crown 2 days after bleaching. The panels represent the group treated with bleaching gel, commercial product (G3) for 45 minutes and the control group at magnifications of 40x and 100x. DETAILED DESCRIPTION

[0019] The present technology relates to products for tooth whitening based on the in situ generation of active oxygen in the form of oxygen free radical species. The whitening gel comprises a modified niobium compound and its activity is primarily maximized when it is applied together with a low concentration of 1% to 10% (preferably 3% by mass) hydrogen peroxide and stabilized with a thickener (preferably carbopol). The whitening gel can be used for teeth whitening without the need for additional light treatment, which makes it more effective than commercial products when used in teeth whitening and has significant potential to reduce side effects (allergy and inflammation). The developed product showed no cytotoxicity and no significant inflammatory effects were observed in dental pulp tissue. The present technology also describes a method for preparing the whitening gel.

[0020] The tooth whitening gel comprises a niobium compound modified by reacting with a peroxide in advance and a thickener, the ratio of the niobium compound to the thickener being between 1% by mass and 50% by mass.

[0021] The thickening agent used may be selected from the group comprising cellulose hydroxyethyl ether, xanthan gum, hydroxymethyl cellulose, carbomer, carbopol or a combination thereof, or toothpaste or pure glycerin.

[0022] The niobium compound used may be selected from the group consisting of niobium phosphate, niobium oxide, acetate, chloride, niobium filter cake, niobium oxide, or its oxalate anion ([Nb(O)(C2O4)3] 3- ).

[0023] The peroxide used may be chosen from the group consisting of methyl ethyl ketone peroxide, benzoyl peroxide, urea peroxide, or hydrogen peroxide, with a purity between 30% and 70%, and a concentration between 1.0% and 10.0% m / m of peroxide relative to the total mass of the gel (thickener and niobium compound).

[0024] The method for preparing the teeth whitening gel comprises the following steps:

[0025] a modified niobium compound, by reacting with hydrogen peroxide having a purity between 30% and 70% to produce surface oxide groups, the peroxide concentration used being between 1.0% and 10.0% m / m relative to the total mass (thickener and niobium compound);

[0026] b. adding a thickener at a ratio of 1% to 10% by mass of the modified niobium compound obtained in step "a" relative to the thickener;

[0027] c. Mix the composition obtained in "b" at room temperature under gentle shaking between 50 rpm and 1000 rpm for a time interval of 10 minutes to 60 minutes.

[0028] In step "a", the niobium compound is selected from the group consisting of niobium phosphate, niobium oxide, acetate, chloride, niobium filter cake, niobium oxide, or its oxalate anion ([Nb(O)(C2O4)3] 3- ).

[0029] In step "a", the peroxide is selected from the group comprising methyl ethyl ketone peroxide, benzoyl peroxide, urea peroxide or hydrogen peroxide.

[0030] In step "b", the thickening agent is selected from the group comprising cellulose hydroxyethyl ether, xanthan gum, hydroxymethyl cellulose, carbomer, carbopol or a combination thereof, or toothpaste or pure glycerin.

[0031] Tooth whitening gels can be used to prepare formulations for teeth whitening.

[0032] The following examples describe certain aspects of the technology and should not be considered limiting.

[0033] Example 1 - Obtaining a whitening gel from a reactive compound containing niobium and active oxygen

[0034] By mixing carbopol with niobium compounds, oxalate [Nb(O)(C2O4)3] 3- to obtain a whitening gel, but the niobium compound may be niobium pentoxide, niobic acid, niobium phosphate or, alternatively, niobium oxyhydroxide.

[0035] The niobium compound is modified with commercial hydrogen peroxide (35% v / v) to a concentration of 3% by mass of peroxide relative to niobium and carbopol in the whitening gel. Commercial carbopol is added to obtain a gel with a 1% by mass ratio of niobium compound relative to carbopol. It is important to emphasize the stabilization of the whitening gel by the presence of carbopol, which, in addition to providing viscosity to the gel, also stabilizes the formed oxidized groups. The reactive species (oxygen radicals) are formed according to the following three chemical reactions:

[0036] -Nb-OH+H2O2→-Nb-OOH+H2O (1)

[0037] -Nb-OOH→-Nb-O*+*OH (2)

[0038] -Nb-O*+H2O→-Nb-OH+*OH (3)

[0039] The resulting gel was maintained under gentle shaking for 40 minutes. Figure 1 A photograph of the resulting final gel containing active oxygen species ready for use in a tooth whitening agent is shown.

[0040] Example 2 - Tooth Whitening Test in the Presence of Low H2O2 Content (2% m / m)

[0041] Twelve bovine teeth that had been cleaned and stored in a thymol solution (0.1%) were selected. The teeth were randomly divided into 6 groups (n=2) and appropriately labeled (Table 1). The initial buccal shade of the middle third of each tooth was determined using a VITA Easy Shade spectrophotometer (VITA, Bad Sackingen, Germany). The tooth whitening levels were compared with VITA 3D Master sample cards (Vita, Bad Sackingen, Germany). Photos of bovine teeth before and after tooth whitening were recorded using a Canon T6i camera, macro 100mm, manual mode, shutter speed 1 / 160, aperture 5.0, ISO 1600, without using a flash.

[0042] Table 1: Composition of materials used for tooth whitening

[0043]

[0044] The bleaching tests were carried out using hydrogen peroxide as bleaching agent and niobium compounds. A commercial product for teeth whitening (whitening grade 6%, FGM) commonly used at home or under the supervision of a dentist was tested as a comparison. For the teeth whitening test, the buccal surface of each specimen was covered with a layer containing 4.0 g of a mixture of carbopol gel, 1% of a niobium compound and an equal amount of 2% of hydrogen peroxide. The application of the materials was carried out for 30 minutes, 60 minutes, 90 minutes and 120 minutes in the absence of light radiation, and at the end of each application, the color of the teeth was measured using a VITA Easy Shade spectrophotometer. After 120 minutes, hydration was evaluated, wherein the teeth were immersed in water for another 30 minutes.

[0045] Figure 2 The results of tooth whitening are shown, expressed by the parameters of lightness, color intensity / lightness and hue obtained with the VITA 3D MASTER sample card.

[0046] In addition, the effect of teeth whitening on bovine teeth was qualitatively observed using images obtained by a photographic camera. Figure 3 Images are shown in , which show the effect of applying materials G1 and G3 on teeth.

[0047] The G1 group showed the best results compared to the other groups; color change was detected already from the 30-minute evaluation. One score was used for the lightness parameter and one score was used for the brightness parameter. In the evaluation 60 minutes after the application of the teeth whitening gel, lightness increased by one point and lightness increased by two points. This bleaching level was stable until the last application, for a total of 120 minutes ( Figure 2 ). As expected, the hue parameter is not changed.

[0048] The catalyst using a chemical pre-treatment (G2) showed a lower efficiency in the tooth whitening process when compared to G1. The only recorded bleaching evolution was of only one point in the lightness parameter. The treatment of the solid with hydrogen peroxide produces reactive oxygen species through the interaction of the Bronsted acid sites (Nb-OH) or Nb=O groups present on the surface of the niobium compound with H2O2. In both materials (G1 and G2), the formation of these species occurs, but the oxidizing groups are formed in situ, as in G1, which enhance the tooth whitening by effectively oxidizing the dye molecules responsible for the tooth color. G3 presented a whitening evolution in the lightness and lightness parameters with 3 and 1 points, respectively. The change in the hue parameter (1 point) is not significant for the assessment of the bleaching level, as can also be seen in Figure 3 It can be seen in.

[0049] The results of tooth whitening using the tooth whitening gel of the present invention, in the presence of hydrogen peroxide (2%), were similar to those achieved using the commercial product FGM, which has a higher concentration of hydrogen peroxide (6%). Gel G1, which demonstrated the best tooth whitening performance, was tested in the presence of different hydrogen peroxide concentrations, including 0.5% and 1%. By varying the concentration of the bleaching agent in the material, it was found that a 2% concentration (G1) maximized the tooth whitening effect, making it more effective than the commercial material. Lower concentrations of H₂O₂, 0.5% and 1%, showed less pronounced results, with bleaching levels of approximately 2 points, thus being less effective than the commercial product. The amount of reactive oxygen groups formed in situ is directly dependent on the amount of hydrogen peroxide added to the material, as low concentrations limit the formation of reactive species and therefore reduce the efficiency of tooth whitening.

[0050] The present invention demonstrates that gels formed using niobium compounds exhibit a high ability to remove stains in a shorter application time than commercial products. For comparative purposes, tooth whitening tests were also conducted in the absence of niobium compounds, and the results showed ineffective bleaching. Low concentrations of hydrogen peroxide are insufficient for whitening teeth, and the presence of a niobium catalyst is necessary to enhance the decomposition of hydrogen peroxide, which forms reactive oxygen species in situ for effective tooth whitening.

[0051] It should be noted that the present invention uses lower amounts of hydrogen peroxide in a teeth whitening method than commercial products widely used by dentists, with the significant potential to reduce side effects during treatment. This fact is of high clinical relevance, as the indiscriminate use of high concentrations of peroxide and prolonged application times can cause undesirable damage to tooth structure, ranging from increased sensitivity to pulp necrosis or degradation of the enamel crystal structure.

[0052] Example 3 - In vivo study of the effects of niobium-containing tooth whitening gel on tooth enamel and pulp

[0053] Scanning electron microscopy (SEM) images were obtained to evaluate the effects of tooth whitening agents on tooth enamel. The evaluated teeth were extracted from rats and treated for 45 minutes with a tooth whitening gel material containing niobium (G1), a commercial material (G3), and a control group consisting of teeth not treated with a tooth whitening agent.

[0054] exist Figure 4Cracks in the tooth enamel can be noticed in all images (including the control group). This behavior is normal in rat teeth, which are more sensitive than human teeth, and the effect may be less pronounced in human teeth. The EDS spectra show the presence of the elements Ca, O, P, C, Na, Cl, K and Mg in all teeth. The teeth to which the niobium-containing tooth whitening gel (G1) was applied presented Ca / O and Ca / P ratios of 2.9 and 2.3, respectively. These values ​​are higher than those observed for teeth subjected to commercial tooth bleaching (G3), which presented Ca / O=1.5 and Ca / P=2.1, as well as those observed for the control group, where Ca / O=1.2 and Ca / P=1.95. These results show that the use of the niobium-containing tooth whitening gel as a tooth whitening agent does not damage the chemical composition of the teeth and therefore does not cause their demineralization. Therefore, it can be said that the developed material has no aggressive effect on tooth enamel.

[0055] To evaluate the changes in the dental pulp, histological examinations were performed on the teeth of rats after tooth whitening with materials G1 (teeth whitening gel containing niobium), G3 (commercial), and a control group. The procedures for working with animals were carried out in accordance with the biosafety standards and recommendations of the Ethical Committee of the Federal University of Minas Gerais (CETEA). Images obtained from the tests conducted with rats from the Rattus norvegicus group are shown in Figure 1. Figure 5 shown.

[0056] All species in this group showed significant changes in the dental pulp tissue. Images revealed a significant number of inflammatory cells in the pulp tissue of rats treated with a commercial product containing a higher concentration of H₂O₂. Furthermore, the odontoblast layer in this group was more disorganized, suggesting a greater involvement of the inflammatory process. Inflammation was less pronounced in rats treated with the currently developed material, displaying similar findings to the control group. Furthermore, as observed in the control group, the odontoblast layer remained intact.

Claims

1. A teeth whitening gel comprising niobium oxalate modified by reacting with hydrogen peroxide in advance and carbomer, wherein the ratio of the niobium oxalate to the carbomer is between 1% by mass and 50% by mass.

2. A method for preparing the tooth whitening gel according to claim 1, comprising the steps of: a) modifying the niobium oxalate with hydrogen peroxide having a purity between 30% and 70%, the concentration of hydrogen peroxide used being between 1.0% and 10.0% m / m relative to the total mass; b) adding the carbomer at a ratio of 1% to 10% by mass of the modified niobium oxalate obtained in step "a" relative to the carbomer; c) Mixing the composition obtained in "b" at room temperature under gentle shaking between 50 rpm and 1000 rpm for a time interval of 10 minutes to 60 minutes.

Images