Dental whitening gel comprising modified niobium compounds, process and use.

Abstract

Dental whitening gel comprising modified niobium compounds, process and use. The present technology refers to a product applied to dental whitening based on the generation of active oxygen in the form of oxygen radical species in situ. The whitening gel comprises modified niobium compounds and its activity is maximized mainly if it is applied with hydrogen peroxide in low concentrations, from 1 to 10% (preferably 3% by mass), with stabilization by a thickener, preferably carbopol. The whitening gel can be used in dental whitening without the need for supplemental light, which allows its use in dental whitening with superior efficiency to commercial products and with significant potential for reducing side effects (hypersensitivity and inflammation). The developed product did not show cytotoxicity, and no significant inflammatory effect was observed in the pulp tissue.The present technology also describes a process for producing the whitening gel.

Description

1 / 13 “DENTAL WHITENING GEL COMPRISING MODIFIED NIOBIUM COMPOUNDS, PROCESS AND USE”

[01] The present technology relates to a product applied to dental whitening based on the generation of active oxygen in the form of oxygen radical species in situ. The whitening gel comprises modified niobium compounds and its activity is maximized mainly if it is applied with hydrogen peroxide in low concentrations, from 1 to 10% (preferably 3% by mass), with stabilization by a thickener, preferably carbopol. The whitening gel can be used in dental whitening without the need for supplemental light, which allows for use in dental whitening with superior efficiency to commercial products and with significant potential for reducing side effects (hypersensitivity and inflammation). The developed product did not show cytotoxicity, and no significant inflammatory effect was observed in the pulp tissue. The present technology also describes a process for producing the whitening gel.

[02] In recent years, there has been a significant increase in demand for teeth whitening in aesthetic clinics and dental offices. However, commercial products such as whitening gels or bleaching agents use high concentrations (6 to 35%) of hydrogen peroxide (H2O2) in their formulations. Exposure of teeth to peroxide can cause side effects such as sensitivity, damage to the pulp, enamel, and periodontal tissue. In the state of the art, several studies highlight the importance of minimizing these adverse effects by using materials based on inorganic compounds (Application of Titanium Dioxide Nanotubes to Tooth Whitening, Nano Biomedicine, Volume 6, Issue 2, 12 December 2014, Pages 63-72) (Synthesis of metal ion-histidine complex functionalized mesoporous silica nanocatalysts for enhanced light. Petition 870200151388, dated 01 / 12 / 2020, page 3 / 16 2 / 13 free tooth bleaching, Acta Biomaterialia, Volume 7, Issue 5, 7 January 2011, Pages 2276-2284)

[03] In the state of the art, it is also possible to find several studies highlighting the use of niobium compounds for use in 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).

[04] The use of reactive materials in dental bleaching is reported in the literature in different documents. The document US20040180008, from 2004, entitled “Dental bleaching agent kit and the method for bleaching teeth” and US20060222604, from 2002, with the following title “Method for bleaching teeth and bleaching agent for teeth” report the combined use of titanium compounds and visible light based on the photocatalytic reaction. In addition, the importance of using peroxides to ensure dental bleaching is highlighted.

[05] The invention related to US patent 5645428, of 1995, entitled “Method for whitening teeth” reports the efficiency of teeth whitening using a mixture of peroxides with different catalysts exposed to argon laser radiation and also with carbon dioxide laser. This method employs other materials including buffers, stabilizers, desensitizers and thickeners.

[06] In US patent 5032178, from 1990, entitled “Dental composition system and method for bleaching teeth”, materials from the manganese sulfate and iron sulfate classes that were employed are described. Petition 870200151388, dated 01 / 12 / 2020, page 4 / 16 3 / 13 along with other products, including hydrogen peroxide and the presence of visible radiation in teeth whitening.

[07] Document BR102013027175-6, filed in 2013, entitled “Dental whitening accelerator”, refers to a mixture of ferric nitrate and cupric nitrate together with hydrogen peroxide promoting efficient whitening.

[08] Natural catalysts such as enzymes from the peroxidase family, such as catalase, are described in document BR102014010685-5, filed in 2014, entitled “Maximizer of dental whitening”, possessing a rapid decomposition of hydrogen peroxide or carbamide peroxide with efficient whitening action on teeth.

[09] Document PI0801862-6, from 2008, entitled “Dental whitening gel with energy-absorbing and thermally conductive solid micro or nanoparticles”, refers to conductive inorganic, ceramic or organic micro or nanoparticles that are incorporated into peroxide-based whitening gel which, in addition to providing greater efficiency in dental whitening, minimizes side effects such as hypersensitivity.

[010] The use of materials based on niobium compounds, highlighting the novel use of the oxalate salt (which may be niobium pentoxide, niobic acid, and oxyhydroxide) in the activation of hydrogen peroxide or organic peroxides, as proposed in the present technology, applied to dental whitening, is novel, mainly due to the in situ generation of oxygen radicals due to the reaction of niobium with H2O2, as well as the stabilization of oxygen species with commercial carbopol. Another novelty of the present invention is that the added hydrogen peroxide is decomposed by reaction with niobium species, generating active oxygen species, thus reducing the presence of free peroxide and causing sensitivity to be reduced. Petition 870200151388, dated 01 / 12 / 2020, page 5 / 16 4 / 13 eliminated. In this way, it is possible to reduce the side effects of hypersensitivity during treatment, in addition to allowing the production of a low-cost material, which can facilitate its commercialization.

[011] The oxygen species generated in the dissociation of H2O2 have an oxidizing action capable of breaking the chemical bonds of the molecular chains of chromophore groups (substances that give color to teeth). Low concentrations of peroxide are sufficient for this effect (approximately 2% by mass) in the product presented due to three technological innovations: (i) the niobium compound acts efficiently and quickly in its activation to generate reactive radical species; (ii) reduction of free peroxide, decreasing sensitivity during whitening; (iii) carbopol stabilizes the radicals, preventing their decomposition, which enhances dental whitening.

[012] Furthermore, with the use of this gel in teeth whitening there is no need to use radiation to decompose the peroxide, a significant change in pH, and thus it is possible to reduce the treatment time in the office or at home. These characteristics make the product, generated in the present technology, with great commercial potential.

[013] The present technology deals with the development of material using niobium sources as raw material for obtaining whitening nanoparticles. The use of niobium compounds in the production of niobium-containing dental whitening gel, as proposed in the present technology, is not reported in the scientific literature and may promote another commercial application for this important chemical element, which is currently used mainly in the metallurgical industry. BRIEF DESCRIPTION OF THE FIGURES

[014] Figure 1 shows an applicator syringe containing the dental whitening gel. Petition 870200151388, dated 01 / 12 / 2020, page 6 / 16 5 / 13

[015] Figure 2 presents clarity, color intensity / luminosity and hue parameters obtained using the VITA 3D MASTER scale with different niobium compounds.

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

[017] Figure 4 shows SEM images of rat teeth subjected to dental bleaching with bleaching gel G1 (A), commercial G3 (B) and the control group (C) with magnification of 200X (top figures) and 500X (bottom figures).

[018] Figure 5 presents representative images of hematoxylin and eosin stained sections showing the coronal pulp 2 days after bleaching. The panels represent the groups treated with the bleaching gel, the commercial product (G3) for 45 minutes, and the control group, with 40x and 100x magnification. DETAILED DESCRIPTION OF THE TECHNOLOGY

[019] The present technology relates to a product applied to dental whitening based on the generation of active oxygen in the form of oxygen radical species in situ. The whitening gel comprises modified niobium compounds and its activity is maximized mainly if it is applied with hydrogen peroxide in low concentrations, from 1 to 10% (preferably 3% by mass), with stabilization by a thickener, preferably carbopol. The whitening gel can be used in dental whitening without the need for supplemental light, which allows for use in dental whitening with superior efficiency to commercial products and with significant potential for reducing side effects (hypersensitivity and inflammation). The developed product did not show cytotoxicity, and no significant inflammatory effect was observed in the pulp tissue. The present technology also describes a process for producing the whitening gel. Petition 870200151388, dated 01 / 12 / 2020, page 7 / 16 6 / 13

[020] The dental whitening gel comprises niobium compounds modified by prior reaction with peroxides and a thickener, in a proportion between 1 and 50% by mass of the niobium compound in relation to the thickener.

[021] The thickener used may be selected from the group comprising natrosol, xanthan gum, hydroxymethylcellulose, carbomer, carbopol or combinations thereof, or toothpaste or pure glycerin.

[022] The niobium compounds used may be selected from the group comprising niobium phosphates, niobium oxides, acetates, chlorides, niobium filter cake, niobium, or the oxalate anion ([Nb(O)(C2O4)3]3-).

[023] The peroxides used may be selected from the group comprising methyl ethyl ketone peroxide, benzoyl peroxide, carbamide peroxide or hydrogen peroxide, with a purity between 30 and 70%, at concentrations between 1.0 and 10.0 m / m of peroxide relative to the total mass of the gel (thickener and niobium compound).

[024] The process of preparing the dental whitening gel comprises the following steps: a. Modify niobium compounds, generating surface oxidizing oxygen groups by reaction with hydrogen peroxide of purity between 30 and 70%, using peroxide concentrations between 1.0 and 10.0% w / w relative to the total mass (thickener and niobium compound); b. Add the thickener in a proportion of 1 to 10% by mass of the modified niobium compound obtained in step “a” in relation to the thickener; c. Mix the mixture obtained in “b” under gentle stirring between 50 and 1000 rpm for a period of 10 to 60 minutes, at room temperature. Petition 870200151388, dated 01 / 12 / 2020, page 8 / 16 7 / 13

[025] In step “a” niobium compounds are selected from the group comprising niobium phosphates, niobium oxides, acetates, chlorides, niobium filter cake, niobium, or the oxalate anion ([Nb(O)(C2O4)3]3-).

[026] In step “a” the peroxides are selected from the group comprising methyl ethyl ketone peroxide, benzoyl peroxide, carbamide peroxide or hydrogen peroxide.

[027] In step “b” the thickeners are selected from the group comprising natrosol, xanthan gum, hydroxymethylcellulose, carbomer, carbopol or combinations thereof, or toothpaste or pure glycerin.

[028] Dental whitening gel can be used to prepare formulations for teeth whitening.

[029] The following examples describe aspects of the present technology and should not be considered as limiting. EXAMPLE 1 - Obtaining the whitening gel from the active niobium compound containing active oxygen.

[030] The whitening gel is obtained by mixing carbopol with the niobium compound, preferably the oxalate, [Nb(O)(C2O4)3]3-, but it can also be niobium pentoxide, niobic acid, niobium phosphate or even niobium oxyhydroxide.

[031] The niobium compounds were modified with commercial hydrogen peroxide (35% V / V) so that in the bleaching gel the concentration is 3% by mass of peroxide relative to niobium and carbopol. Commercial carbopol was added to obtain a gel in a 1% by mass ratio of niobium compound relative to carbopol. It is important to emphasize that the bleaching gel is stabilized by the presence of carbopol, which, in addition to providing the gel's consistency, stabilizes the oxygen radicals formed. The reactive species (oxygen radicals) are formed according to the following three chemical reactions: Petition 870200151388, dated 01 / 12 / 2020, page 9 / 16 8 / 13 -Nb-OH + H2O2 ^ -Nb-OOH + H2O(1) -Nb-OOH ^ -Nb-O* + *OH(2) -Nb-O* + H2O ^ -Nb-OH + *OH(3)

[032] The resulting gel was kept under gentle agitation for 40 min. Figure 1 shows a photograph of the final gel obtained containing the active oxygen species ready for use as a dental bleaching agent. EXAMPLE 2 - Tooth whitening tests in the presence of low H2O2 content (2% w / w)

[033] Twelve bovine teeth were selected, cleaned, and preserved in a thymol solution (0.1%). The teeth were randomly divided into 6 groups (n=2) and properly identified (Table 1). The initial color of the vestibular surface for the middle third of each tooth was determined using the VITA Easy Shade spectrophotometer (VITA, Bad Sackingen, Germany). The whitening levels of the teeth were compared to the VITA 3D Master scale (Vita, Bad Sackingen, Germany). Photographs of the bovine teeth were taken before and after dental whitening using a Canon T6i camera, 100mm macro lens, manual mode, 1 / 160 shutter speed, f / 5.0 aperture, ISO 1600, without the use of flash. Table 1: Composition of materials used in teeth whitening. Composition Group G1 Carbopol, catalyst (niobium compound), hydrogen peroxide (2%). G2 Carbopol, catalyst (niobium compound previously treated with hydrogen peroxide), hydrogen peroxide (2%). G3 Commercial product - White Class 6% (H2O2), FGM. Petition 870200151388, dated 01 / 12 / 2020, page 10 / 16 9 / 13

[034] Whitening tests were performed using hydrogen peroxide as a whitening agent and niobium compounds. A commercial dental whitening product (White Class 6%, FGM), normally used at home or under the supervision of a dentist, was tested as a comparison. For the dental whitening test, the buccal surface of each specimen was covered with a layer of the mixture containing 4.0g of Carbopol gel, 1% of the niobium compound, and an equivalent amount of 2% hydrogen peroxide. The material was applied for 30, 60, 90, and 120 minutes in the absence of light radiation, and at the end of each application, the tooth color was measured using the VITA Easy Shade spectrophotometer. After 120 minutes, the effect of hydration was evaluated by immersing the teeth in water for an additional 30 minutes.

[035] Figure 2 shows the results of tooth whitening, which are represented by the parameters of clarity, color intensity / luminosity and shade obtained using the VITA 3D MASTER scale.

[036] In addition, the effect of dental bleaching on bovine teeth was qualitatively observed using images obtained by a photographic camera. The images showing the effect of applying materials G1 and G3 to the teeth are presented in Figure 3.

[037] Group G1 showed the best results compared to the others, with a color change detected as early as the 30-minute assessments. One point for the clarity parameter and one point for the luminosity parameter. In the assessment after 60 minutes of application of the dental whitening gel, there was a gain of one more point for clarity and two for luminosity. This level of whitening stabilized until the last application, totaling 120 Petition 870200151388, dated 01 / 12 / 2020, page 11 / 16 10 / 13 minutes (Figure 2). For the hue parameter, there was no change, as expected.

[038] Catalysts with prior chemical treatment (G2) showed lower efficiency in the tooth whitening process when compared to G1. The only recorded improvement in whitening was just one point in the brightness parameter. Treatment of the solid with hydrogen peroxide generates reactive oxygen species through the interaction of 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 in situ formation of oxygen groups, as occurs in G1, enhances tooth whitening through the efficient oxidation of the dye molecules responsible for the tooth color. G3 showed an improvement in whitening in the brightness and luminosity parameters, 3 and 1 points respectively. The recorded change in the shade parameter (1 point) was not significant for evaluating the level of whitening, as can also be observed in Figure 3.

[039] The results of tooth whitening using the dental whitening gel of the present invention, in the presence of hydrogen peroxide (2%), are similar to whitening using the commercial product FGM which has a higher concentration of hydrogen peroxide (6%). The gel that showed the best performance for tooth whitening, G1, was tested in the presence of different concentrations of hydrogen peroxide, including 0.5 and 1%. By varying the concentration of the whitening agent in the materials, it was found that the 2% concentration (G1) maximized the tooth whitening effect, being more efficient than the commercial material. Lower concentrations of 0.5 and 1% H2O2 showed less expressive results, around 2 points in the whitening level, and were therefore less effective than the Petition 870200151388, dated 01 / 12 / 2020, page 12 / 16 11 / 13 commercial product. The reactive oxygen groups formed in situ depend directly on the amount of hydrogen peroxide added to the material, since low concentrations limit the formation of reactive species and consequently the efficiency of tooth whitening is reduced.

[040] The present invention shows that the gel formed with the niobium compound exhibited a high capacity for pigment removal in a shorter application time when compared to the commercial product. For comparison, dental whitening tests were also performed in the absence of the niobium compound, and the results showed that the whitening action was inefficient. Hydrogen peroxide at low concentrations is not sufficient to whiten teeth, and the presence of the niobium catalyst is essential to enhance the decomposition of hydrogen peroxide, forming reactive oxygen species in situ to act efficiently in dental whitening.

[041] It should be noted that the present invention employs a lower quantity of hydrogen peroxide in the dental whitening process than commercial products widely used by dentists, with significant potential for reducing the side effects of the treatment. This fact is of high clinical relevance, as the indiscriminate use of high concentrations of peroxides and prolonged application times can cause undesirable damage to the dental structure, ranging from increased sensitivity to pulp necrosis or degradation of the enamel's crystalline structure. EXAMPLE 3 - In vivo study of the effect of niobium-containing dental whitening gel on tooth enamel and pulp.

[042] In order to evaluate the effect of the dental bleaching agent on tooth enamel, scanning electron microscopy images were obtained. Petition 870200151388, dated 01 / 12 / 2020, page 13 / 16 12 / 13 (SEM). The teeth evaluated were extracted from rats subjected to dental bleaching treatment with niobium dental bleaching gel (G1), commercial (G3) for 45 minutes and with the control group, which consists of teeth that were not subjected to dental bleaching treatment.

[043] In all images in Figure 4, it is possible to observe fissures in the tooth enamel, including in the control group. This behavior is normal in rat teeth, which are more sensitive than human teeth, and the effect on human teeth will probably be less pronounced. EDS spectra show the presence of the elements Ca, O, P, C, Na, Cl, K, and Mg in all teeth. Teeth treated with the niobium-containing dental whitening gel (G1) have Ca / O and Ca / P ratios of 2.9 and 2.3, respectively. These values ​​are higher than those observed for the tooth treated with the commercial dental whitening gel (G3), which showed Ca / O=1.5 and Ca / P=2.1, and also higher than those observed for the control, in which Ca / O=1.2 and Ca / P=1.95. These results show that the use of niobium-containing dental whitening gel does not harm the chemical composition of teeth, and consequently does not cause demineralization.Therefore, it can be stated that the developed material does not have an aggressive effect on tooth enamel.

[044] To evaluate changes in the dental pulp, histological examinations were performed on rat teeth after they underwent dental bleaching using materials G1 (dental bleaching gel containing niobium), G3 (commercial) and the control group. The procedure for working with the animals was carried out respecting biosafety standards and recommendations of the Ethics Committee of the Federal University of Minas Gerais (CETEA). From the tests performed with the rats of the Rattus No vergicus group, the images obtained are shown in Figure 5. Petition 870200151388, dated 01 / 12 / 2020, page 14 / 16 13 / 13

[045] All species in this group exhibited significant changes in the coronal pulp tissue. Images showed a considerable amount of inflammatory cells in the pulp tissue of rats subjected to dental bleaching with the commercial product, containing a higher concentration of H2O2. In addition, the odontoblastic layer is more disorganized in this group, indicating more aggressive effects in the inflammatory process. Inflammation was not significant in rats that underwent bleaching with the developed material, exhibiting behavior similar to the control. Furthermore, the odontoblastic layer was not altered, remaining intact, as observed in the control group. Petition 870200151388, dated 01 / 12 / 2020, page 15 / 16

Claims

1 / 1 CLAIMS 1. DENTAL WHITENING GEL characterized by comprising niobium compounds selected from the group comprising niobium oxalate or niobium pentoxide or niobic acid or niobium phosphate or niobium oxyhydroxide modified by prior reaction with hydrogen peroxide and thickener carbopol, in the proportion between 1 and 10% by mass of the modified niobium compound, in relation to carbopol.

2. PROCESS FOR PREPARING THE DENTAL WHITENING GEL defined in claim 1, characterized by comprising the following steps: a) Modifying niobium oxalate or niobium pentoxide or niobic acid or niobium phosphate or niobium oxyhydroxide with hydrogen peroxide of purity between 30 and 70%, using hydrogen peroxide concentrations between 1.0 and 10.0% w / w relative to the total mass (thickener and niobium compound); b) Adding the thickener carbopol in a proportion of 1 to 10% by mass of the modified niobium compound obtained in step “a” relative to the carbopol; c) Mixing the composition obtained in “b” under gentle stirring between 50 and 1000 rpm for a time interval between 10 and 60 min, at room temperature.

3. USE OF THE DENTAL WHITENING GEL defined in claim 1, characterized by being for preparing formulations for teeth whitening. Petition 870250071075, dated 12 / 08 / 2025, page 10 / 10

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