BR102022002275A2 - COMPOSITION OF SOLID TOOTHPASTE FOR TREATMENT, ORAL HYGIENIZATION AND REGENERATION OF ORAL SOFT TISSUE - Google Patents

Abstract

The present invention deals with an oral dentifrice composition in tablet format capable of simultaneously promoting oral hygiene - performing antibacterial, antifungal, aseptic, anticaries, antitartar activities - and targeted dental treatment - recovery from surgical processes, maintenance and care of implants, among others. The composition comprises at least one carrier, a surfactant, an abrasive, an active ingredient and a herbal agent. Additionally, the composition may comprise one or more sweeteners, flavorings, stabilizers, preservatives, among other components aimed at optimizing the physicochemical properties, comfort of use, therapeutic and hygiene efficacy.

Description

COMPOSITION OF SOLID TOOTHPASTE FOR TREATMENT, ORAL HYGIENIZATION AND REGENERATION OF ORAL SOFT TISSUE TECHNOLOGICAL FIELD OF THE INVENTION

[001] The present invention falls within the field of oral hygiene products, more specifically in the field of solid dentifrices aimed at anti-caries, anti-tartar treatment, regeneration of oral soft tissues, oral hygiene, remineralization, healing and oral asepsis.

[002] In particular, the invention falls within the field of solid toothpastes in tablet format containing active ingredients and herbal agents as therapeutic ingredients.

STATE OF THE TECHNIQUE

[003] It is indisputable that the only scientifically proven method for preventing various oral diseases lies in the association of: quality oral hygiene products specific to the needs of each patient; adequate guidance of the individual regarding brushing techniques and appropriate use of dental floss and mouthwash; and periodic return to the dental office.

[004] Even though the main oral diseases are multifactorial and may be of systemic origin or derived from adverse habits, the literature presents a consensus regarding the efficiency of preventing caries, gingival, periodontal and peri-implant diseases. To this end, it is essential that the dentist is able to carry out an individualized diagnosis of each patient's needs in relation to the various relevant aspects of their oral health, such as the presence of bleeding, thermal sensitivity, presence of caries lesions or not carious, appropriate type of treatment and cleaning capacity, among others.

[005] Taking into account the complexity mentioned above, it is inconceivable to defend the thesis that the same oral hygiene product (solid dentifrice, gel or cream, or mouthwash) can act equally effectively for patients with different profiles and care practices. completely different mouthpieces. For example, patients with intact dentition, composite resin restorations or who have received osseointegratable implants, present completely different clinical needs, and such particularities must be considered when choosing the product.

[006] The type of product most used to provide oral health care is certainly toothpaste. These are traditionally made up of compositions presented in gel or cream form intended for oral hygiene, generally consisting of formulations that combine a number of fundamental substances that make up the body of the product with thickening, abrasive, humectant, preservative, sweetener, flavoring and foaming purposes. , in addition to water.

[007] Its main purposes are oral cleaning, including teeth and soft tissues, polishing of restorations and teeth, removal of debris and bacterial biofilm and tissue regeneration, in addition to the prevention of periodontal and peri-implant diseases and dental caries.

[008] The basic composition of toothpastes comprises: a. thickener, which may be one or more gel-forming substances such as cellulose derivatives, gums (guar and xanthan) and thickening silicas; B. abrasive agent, insoluble substances such as calcium carbonate and calcium phosphate, zirconium silicate, alumina and silica abrasive; w. surfactants such as sodium lauryl sulfate, sodium lauroylsarcosinate, poloxamer or cocoamido propylbetaine; d. wetting agents, glycerin, sorbitol, propylene glycol or polyethylene glycol 400; It is. sweeteners: saccharin, cyclamate, stevia and xylitol and also various flavors; f. preservatives: parabens and benzoates, which are also basic components.

[009] In addition to the aforementioned components, toothpastes may additionally contain coloring agents and purpose-based agents.

[0010] The vast majority of toothpastes disclosed in the state of the art consist of products for generic application, designed for oral hygiene, without adding any therapeutic purpose or even paying attention to particular clinical profiles. Due to the lack of customization of available products, consumers often end up purchasing products that are not suitable for their dental profile, or even the dental professional themselves find themselves without suitable product options to recommend to the patient.

[0011] Let us take as an example of such a problem the case of the use of abrasives. It is common knowledge in the technical field that abrasives, while they can be effective for the mechanical disorganization of dental biofilm, can generate unnecessary and critical wear for patients with non-carious cervical lesions. Therefore, a bad sanitizer should use a product with greater abrasiveness (RDA 100-120), since the frequency and duration of cleaning sessions will be lower, and abrasion must be increased to provide adequate oral cleaning. On the other hand, a patient with tooth sensitivity should receive care with products with lower abrasiveness (RDA 50-70), as excessive abrasion can accentuate tooth sensitivity. Similarly, a patient who has a composite resin restoration should use products with low or very low abrasiveness (RDA 50-70), to avoid excessive wear and prolong the duration of the restoration.

[0012] Just as it is necessary to pay attention to the abrasiveness of the toothpaste to be used by each patient, dental professionals and consumers must also take into account the active and therapeutic principles present in the product's formulation. For example, patients who have undergone a surgical procedure to place a dental implant should prioritize products that include active ingredients aimed at tissue regeneration, healing and oral asepsis.

[0013] From the points above, it can be concluded that the choice and recommendation of a suitable toothpaste is not trivial, and must consider factors such as brushing habits, oral profile, dental history and other factors pertinent to the patient's oral health.

[0014] Despite the known importance of the above factors, there are still no products in the state of the art that combine components capable of simultaneously providing oral hygiene and therapies for specific dental conditions. For this reason, consumers and professionals often have to resort to a combination of different products and/or treatments applied exclusively in a dental office. Therefore, the need for a solution that delivers a balanced combination of hygiene and customizable therapy for different patient profiles is evident.

[0015] In addition to the lack of adequate dental solutions, the use and commercialization of traditional toothpastes in gel form generates high amounts of plastic waste. As a solution to this problem, solid tablet dentifrices were developed, such as disclosed in documents US 2004/0101494, US 10959931, US 10806685, US 2020/0188245, US 6984377. By removing the need for a plastic wrapper (plastic tube) for use of the product, solid toothpastes generate reduced amounts of waste, being a solution more aligned with sustainability and ecological preservation goals.

[0016] However, the solutions revealed in the documents above, despite presenting toothpastes in tablet format, do not have stable and focused compositions for treating dental conditions of patients with different oral profiles. In general, such solutions are restricted to revealing generic application solutions, not presenting ingredients focused on the treatment of specific conditions, such as wound healing, post-operative recovery, cleaning and conservation of dental implants and resin restorations, among others.

[0017] The scarcity of solid toothpaste formulations is related to the difficulty of producing stable compositions from both a chemical and physical point of view. Far from depending on the mere application of current techniques in the field of formulation, the development of solid (or chewable) dentifrices faces the challenge of simultaneously optimizing several aspects: stability, maintenance of acceptable aesthetic standards, pleasant sensorial properties when used in the mouth, effectiveness in oral hygiene, protection and faster tissue restoration, cleaning and conservation of implants and dental restorations, as well as other specific aspects of each application. It is evident, therefore, that this technical problem does not have an obvious solution, requiring intellectual and creative effort.

[0018] The present invention aims to provide a tablet toothpaste with adequate use characteristics, promoting comfort in use (including aspects related to burning, foam volume, flavor and aroma) and adequate dental hygiene, as well as customizable therapeutic characteristics for each patient profile, including mainly components that promote the regeneration and healing of oral soft tissues, reduction of inflammatory responses, reduction of demineralization processes and promotion of remineralization.

SUMMARY OF THE INVENTION

[0019] The present invention aims to provide a solid toothpaste in tablet format that simultaneously comprises functionalities associated with oral hygiene (antibacteria, antifungal, aseptic, anticaries, antitartar) and the treatment of dental conditions (recovery from surgical processes, maintenance and implant care, among others).

[0020] According to the preferred embodiment of the present invention, oral dentifrice composition in tablet format comprising at least one carrier; at least one surfactant; at least one abrasive. The composition further comprises at least one active ingredient and at least one herbal agent.

[0021] According to an embodiment of the invention, the carrier used in the composition is chosen as being at least one of the set comprising: polyvinylpyrrolidone (PVP); lactose; sucrose; dextrose; mannitol; sorbitol; xylitol; erythritol; lactitol; isomalt; maltitol; trehalose; tegatosis; calcium sulfate; bibasic calcium phosphate; tricalcium phosphate; tribasic calcium sulfate; starch, such as corn starch, potato starch, hydrogenated starch hydrolysates and sodium starch glycolate; calcium carbonate; cellulose; modified cellulose, such as microcrystalline cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and hydroxypropylethylcellulose; and their respective mixtures.

[0022] According to the preferred embodiment of the invention, the carrier included in the composition is a binder, which is chosen as being at least one of the set consisting of: cellulose, preferably microcrystalline cellulose, even more preferably microcrystalline cellulose HP 101; sodium starch glycolate; polyvinylpyrrolidone (PVP), more preferably polyvinylpyrrolidone K30 (PVP K30); and hydroxypropylmethylcellulose.

[0023] According to an embodiment of the present invention, the composition comprises hydroxypropylmethylcellulose in an amount of 1-10% by mass.

[0024] According to an embodiment of the present invention, the composition comprises microcrystalline cellulose in an amount of 1-80% by weight.

[0025] In another configuration, the active surfactant of the composition is chosen as being at least one of the set consisting of: sodium lauryl sulfate, lauryl glucoside, amphoteric surfactants in general and amphoteric betaine surfactants. Preferably, the composition comprises the surfactant sodium lauryl sulfate in an amount of 0.5 and 5% by weight, preferably 0.5 to 3% by weight, more preferably 1 to 3%. In a specific configuration of the present invention, the surfactant is sodium lauryl sulfate in an amount of 3%.

[0026] According to an embodiment of the present invention, the composition additionally comprises at least one carrier, said carrier being a lubricant chosen from the set comprising: stearic acid; magnesium and calcium stearate; zinc stearate; hydrogenated and partially hydrogenated vegetable oils (e.g.; peanut oil; castor oil; cottonseed oil; sesame oil; olive oil; corn oil and theobroma oil; Sterotex); animal fats; glycerin; polyethylene glycol; polyoxyethylene monostearate; baby powder; light mineral oils; sodium benzoate; Sodium lauryl sulfate; magnesium oxide and the like and mixtures thereof.

[0027] According to a composition of the present invention, the abrasive of the composition is chosen as being at least one of the set comprising: silicas, including gels, precipitates and amorphous silicas; insoluble sodium polymetaphosphate; hydrated alumina; aluminum hydroxide; aluminum oxide; calcium carbonate; calcium chlorophosphate dihydrate; calcium pyrophosphate; dicalcium phosphate, tricalcium phosphate; calcium polymetaphosphate; boron; sodium and calcium phosphosilicate; emery; grenade; glycine; perlite; pumice stone; Silicon carbide; sodium bicarbonate; zirconium oxide and zirconium silicate and two respective mixtures.

[0028] According to an embodiment of the present invention, the composition has a degree of abrasiveness of 20-150 on the Relative Dentin Abrasivity (RDA) scale, preferably RDA of 30-120, more preferably RDA of 30-100

[0029] In one configuration of the invention, the active ingredient of the composition is chosen as being at least one of the set comprising: hyaluronic acid, monofluorophosphate, dimethylsilanediol salicylate (DSBC) sodium fluoride, xylitol, tetrasodium pyrophosphate, natural essential oils of plants, aqueous, glycolic and alcoholic extracts of plants.

[0030] According to a preferred embodiment of the present invention, the composition comprises hyaluronic acid in the amount of 0.01-10% by mass, preferably 0.01-8% by mass, more preferably 0.01-5%. According to one embodiment of the present invention, the dentifrice composition has 0.2% by weight of hyaluronic acid.

[0031] According to an embodiment of the present invention, the dentifrice composition comprises 0.01% to 5% by weight of the active ingredient dimethylsilanediol salicylate (DSBC), preferably 0.01% and 3%, more preferably between 0.01% and 2%, even more preferably 0.1 and 1.5% by mass. According to a preferred embodiment of the present invention, the dentifrice composition has 0.1% DSBC.

[0032] According to the preferred configuration of the present invention, the composition comprises the active ingredients hyaluronic acid and DSBC.

[0033] According to the configuration of the present invention, the herbal agent of the composition is chosen from the set comprising: green tea extract (Cammelia sinensis), Tea Tree extract (Malaleuca alternifolia) and green propolis (Baccharis dracunculifolia).

[0034] According to the preferred invention, the dentifrice composition comprises green tea extract (Cammelia sinensis) in the amount of 0.110% by mass, preferably 0.1-8% by mass, more preferably 0.1-7% by mass, more preferably 0.1-5%, even more preferably 0.1-1%. According to one embodiment of the present invention, the dentifrice composition has 0.5% by weight of green tea extract (Cammelia sinensis) extract.

[0035] According to an embodiment of the present invention, the dentifrice composition comprises tea tree extract (Melaleuca Alternofilia) in the amount of 0.05-10% by mass, preferably 0.05-10% by mass, more preferably 0. 05-8% by mass, more preferably 0.05-8%, even more preferably 0.01-5%. According to one embodiment of the present invention, the dentifrice composition has 0.1% by weight of tea tree extract (Melaleuca Alternofilia).

[0036] According to the preferred embodiment of the present invention, the dentifrice composition comprises the phytotherapeutic agents green tea extract (Cammelia sinensis) and Tea Tree extract (Malaleuca alternifolia).

[0037] According to a configuration of the invention, the herbal principle can also be chosen from a group comprising natural essential oils and other aqueous, glycolic and alcoholic extracts of plants, not limited to the species Cammelia sinensis, Malaleuca alternifolia and Baccharis dracunculifolia

[0038] The present invention also refers to a process for obtaining a solid pharmaceutical composition (tablet), efficient for oral hygiene and, consequently, for the prevention of dental caries, gingivitis and peri-implant mucositis, which if not controlled can result in worsen leading to periodontal disease and peri-implant disease with tooth or implant loss. The aforementioned composition, after light chewing, followed by brushing the teeth, disintegrates in the saliva, involving the entire dental arch, providing oral hygiene.

[0039] Therefore, the composition claimed here is effective in oral hygiene and in the control of dental caries, gingivitis and their problems. Furthermore, each unit (tablet) contains the exact amount of components necessary for oral hygiene combined with an excellent sensory experience in the mouth. By being kept in a solid state until the moment of use, the present invention avoids interactions between the components of the formulation, maintaining the chemical integrity of its constituents and its effectiveness. Furthermore, the formulation in tablet form provides better portability for the user.

BRIEF DESCRIPTION OF THE FIGURES

[0040] Fig. 1 - Illustration of the experimental design for analysis of differential gene expression depending on the administration of hyaluronic acid and green tea extract in fibroblasts.

[0041] Fig. 2 - Differential expression of the AKT gene in fibroblasts in response to the administration of hyaluronic acid and green tea extract at concentrations of 10%.

[0042] Fig. 3 - Differential expression of the CDK (Cyclin Dependent Kinase) genes, more specifically, of the CDK2, CDK4 and CDK6 genes, in fibroblasts in response to the administration of hyaluronic acid and green tea extract in concentrations of 10%.

[0043] Fig. 4 - Differential expression of the VEFG gene (Vascular Endothelial Growth Factor) in fibroblasts in response to the administration of hyaluronic acid and green tea extract at concentrations of 10%.

[0044] Fig. 5 - Differential expression of the FGF23 and FGFR2 gene (Fibroblast growth factor 23 and Fibroblast growth factor receptor) in fibroblasts in response to the administration of hyaluronic acid and green tea extract in concentrations of 10%.

[0045] Fig. 6 - Summary diagram of the main findings involved in the synergistic effect of hyaluronic acid and green tea extract in the process of oral soft tissue regeneration.

DETAILED DESCRIPTION OF THE INVENTION

[0046] The present invention relates to an oral dentifrice composition in tablet format comprising at least one carrier; at least one surfactant; at least one abrasive. The composition further comprises at least one active ingredient and at least one herbal agent. Additionally, the composition may comprise one or more sweeteners, flavorings, stabilizers, preservatives, among other components aimed at optimizing the physicochemical properties, comfort of use, therapeutic and hygiene efficacy, among other desired aspects.

[0047] Within the scope of the present invention, the term "dentifrice" refers to oral hygiene products, comprising formulations that combine a number of fundamental substances that make up the body of the product for thickening, abrasive, humectant, preservative, sweetening, flavoring purposes. and sparkling wine, in addition to water. They can be in the form of cream or dental gel and have broad purposes recognized by researchers and consumers. Their main purposes are oral cleaning, including teeth and soft tissues, polishing of restorations and teeth, removal of debris and bacterial biofilm and tissue regeneration, in addition to the prevention of periodontal and peri-implant diseases and tooth decay, among other purposes.

[0048] According to the preferred configuration of the present invention, the dentifrice is in solid form, preferably in tablet form. Alternatively, the present composition can be easily adapted to take the form of a gel or cream by applying techniques common to one skilled in the art.

[0049] Within the scope of the present invention, the term "tablet" refers to a solid and small form suitable for chewing and dissolving in a person's mouth. The terms "tablet" are synonymous with: lozenge, pill, bullet, capsule, tablet and any other term that refers to a solid with similar dimensions and with the capacity to dissolve in the oral environment. It should be noted that the synonyms mentioned above are intended only to refer to names popularly used for oral ingestion products, and are not necessarily appropriate technical terms from a regulatory point of view. The appropriate technical synonym for tablet, in harmony with the designations accepted by ANVISA, is “tablet”.

Abrasives

[0050] The term "abrasive” refers to any material capable of providing polishing. Abrasives are responsible for the mechanical disorganization of the bacterial biofilm, cleaning and polishing the natural or artificial tooth surface, in addition to removing extrinsic stains from food pigments or habits, such as smoking.

[0051] It is necessary to highlight that cleaning efficiency and surface wear power depend on the size, shape, hardness and concentration of the abrasive, in addition to the type of brush used (head size, number, shape and distribution of bristles, in addition to the geometry and texture of the filaments that make up the tufts), associated with the pressure exerted and the technique used by the individual. Therefore, it is essential to understand that the correct prescription of toothpaste must be accompanied by a detailed assessment and individualized prescription for each clinical case. Another important aspect to be highlighted is that the type of abrasive used can directly influence the availability of fluorine in the formula, for example, the use of calcium carbonate as an abrasive causes the sodium fluoride (NaF) available during its action to be reduced. lower than that used in its formulation, which may harm the expected clinical results.

[0052] Among the abrasives suitable for use in toothpastes, the following ingredients stand out: silicas, including gels, precipitates and amorphous silicas; insoluble sodium polymetaphosphate; hydrated alumina; aluminum hydroxide; aluminum oxide; calcium carbonate; micronized calcium carbonate calcium chlorophosphate dihydrate; calcium pyrophosphate; tricalcium phosphate; calcium polymetaphosphate; boron; sodium and calcium phosphosilicate; emery; methacrylate; grenade; glycine; perlite; pumice stone; Silicon carbide; sodium bicarbonate; titanium dioxide; zirconium oxide; zirconium silicate and their respective mixtures.

[0053] In cases of aesthetic and functional rehabilitation treatment carried out with ceramic laminates, it is necessary to proceed with a careful selection of oral hygiene products with low or very low abrasiveness, associated with anti-caries, antiseptic and tissue regenerating active ingredients to maintain excellent results in the short, medium and long term. In this sense, the choice of abrasive to be incorporated into the composition of the present invention is crucial, and priority should be given to abrasives with less wear power.

[0054] One of the ways to quantify the abrasiveness of a dentifrice composition is through the Relative Dentin Abrasivity (RDA) scale. According to one embodiment of the present invention, the dentifrice composition has a degree of abrasiveness of 20-150 on the Relative Dentin Abrasivity (RDA) scale, preferably RDA of 30-120, more preferably RDA of 50-120.

[0055] As there are no regulatory definitions on the RDA for tooth creams and gels in Brazil, the present invention was developed based on the values adopted by the American National Standards Institute (ANSI) and American Dental Association (ADA) (Dentifrices - Requirements, Test Methods and Marking, 2013), which has an arbitrary reference value of RDA of 100. According to this scale and classification, toothpastes that have up to 2.5 times the reference value (RDA 250) are considered safe and effective for clinical use.

[0056] According to an embodiment of the present invention, the dentifrice composition comprises the abrasive calcium carbonate in an amount between 10 and 95% by weight, preferably between 50 and 80% by weight, more preferably between 60 and 80%.

[0057] According to another configuration, the dentifrice composition comprises the silica abrasive, preferably Tixosil 43B, in an amount between 1 and 20% by mass, preferably between 1 and 15% by mass, more preferably between 1 and 10%, even more preferably between 3.5 and 6%. According to the specific embodiment of the present invention, the dentifrice composition contains 5% by weight of Tixosil 43B.

[0058] According to the preferred embodiment of the present invention, the composition comprises both calcium carbonate abrasives and Tixosil 43B.

[0059] Tixosil abrasive, also known as silicon dioxide (SiO2) is a micronized silica, acting as a pharmacotechnical adjuvant and an important food additive. Functions as an anti-caking agent, improving the fluidity properties of the powder and the distribution of pharmaceutical ingredients in the formulations; used as a viscosity agent in semi-solid and liquid formulations and as a support for transforming liquids into powders or pastes; improves tablet properties, such as hardness and friability and used as a desiccant to reduce moisture in sensitive active ingredients. Tixosil can also be used as a thickener in liquid, semi-liquid and solid formulations, playing a role in providing greater viscosity and mechanical resistance. Alternatively, Tixosil is also known as Silicon Dioxide; Precipitated Silica; Amorphous Silica; Hydrated Silica; Synthetic Silica; Colloidal silica; CAS number 112926-00-8.

Carriers

[0060] The compositions of this invention also comprise carriers suitable for oral hygiene. As used herein, "carrier suitable for oral hygiene", "oral carrier" or simply "carrier" means one or more compatible solid or liquid diluents or encapsulating substances that are suitable for administration to a subject or suitable for oral administration topical. The term "compatible", as used herein, means that the components of the composition are capable of being mixed with the active ingredient, herbal agents or other essential ingredients, and with each other, in such a manner that there is no interaction that causes a substantial reduction in the effectiveness of the composition when in ordinary use situations. Oral care carriers must, of course, be of sufficiently high purity and sufficiently low toxicity to make them suitable for administration to the subject being treated. Oral care carriers can act to facilitate the incorporation of the active ingredient(s) and/or herbal agent(s) into the dosage form, as well as modify the release rate, stabilize it in the formulation or increase its absorption. Active ingredient(s) and/or herbal agent(s).

[0061] More specifically, the term "carrier suitable for oral hygiene", "oral carrier" or simply "carrier" refers to binders, disintegrating agents, lubricants, stabilizers, foaming agents, chelating agents, buffering agents and preservatives . Binders

[0062] Within the scope of the present invention the term "binder" is any material capable of holding or joining other materials to form a cohesive whole. Binders can also help to form tablets with the necessary mechanical strength. Examples of binders include: polyvinylpyrrolidone ( PVP); lactose; sucrose; dextrose; mannitol; sorbitol; xylitol; erythritol; lactitol; isomalt; maltitol; trehalose; tegatose; calcium sulfate; bibasic calcium phosphate; tricalcium phosphate; tribasic calcium sulfate; starch, such as corn starch , potato starch, hydrogenated starch hydrolysates and sodium starch glycolate; calcium carbonate; cellulose; modified cellulose, such as microcrystalline cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and hydroxypropylethylcellulose; and mixtures thereof.

[0063] In one embodiment of the present invention, the tablet dentifrice composition preferably comprises at least one binder chosen from a group comprising: polyvinylpyrrolidone (PVP); lactose; sucrose; dextrose; mannitol; sorbitol; xylitol; erythritol; lactitol; isomalt; maltitol; trehalose; tegatosis; calcium sulfate; bibasic calcium phosphate; tricalcium phosphate; tribasic calcium sulfate; starch, such as corn starch, potato starch, hydrogenated starch hydrolysates and sodium starch glycolate; calcium carbonate; cellulose; modified cellulose, such as microcrystalline cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and hydroxypropylethylcellulose; and their respective mixtures.

[0064] The choice of the appropriate binder may vary depending on the patient's needs and the active ingredients and/or herbal agents that should be incorporated into the formulation. The precise definition of binders and their concentrations in the composition is not a trivial matter, and the individual activities of the binders and their interactions with other components of the composition must be taken into account.

[0065] According to the preferred embodiment of the invention, the carrier included in the composition is a binder, which is chosen as being at least one of the set consisting of: cellulose, preferably microcrystalline cellulose, even more preferably HP 101 microcrystalline cellulose; sodium starch glycolate; polyvinylpyrrolidone (PVP), more preferably polyvinylpyrrolidone K30 (PVP K30); and hydroxypropylmethylcellulose.

[0066] The binder sodium starch glycolate is a sodium salt of a starch carboxymethyl ether, generally with a molecular weight between 50000011000000. The use of sodium starch glycolate used as a dissolution-promoting excipient in pharmaceutical compositions in tablets, tablets or capsules is already largely in the state of the art. Said ingredient absorbs water quickly, in order to swell the tablet, separating it into smaller fragments. For this reason, sodium starch glycolate is used to accelerate the disintegration of tablets and granules. Sodium starch glycolate can be produced from various starchy foods, for example corn, wheat, rice and potatoes. Sodium starch glycolate can also be designated as sodium starch glycolate, sodium starch glycolate or explosol.

[0067] According to an embodiment of the present invention, the dentifrice composition comprises between 1-20% by mass of the binder sodium starch glycolate, preferably 1-15% by mass, more preferably 1-10%, even more preferably between 5- 10%. According to the specific configuration of the present invention, the dentifrice composition has 8% by weight of sodium starch glycolate.

[0068] HP 101 microcrystalline cellulose binder is a cellulose derivative widely used in pharmaceutical products. This ingredient is commercially available in different particle sizes, types 101 and 102, which have different properties and applications. Microcrystalline cellulose is an excellent diluent for tablets and capsules, presenting free flow. In addition to its function as a binder, microcrystalline cellulose can be used as an adsorbent; diluent; disintegrant; thickener; suspender; viscosifier. Microcrystalline cellulose may also be designated by its CAS number 9004-34-6. Microcrystalline cellulose not only acts as a binder, but also supports the binder in consolidating the compacted system (tablet).

[0069] According to an embodiment of the present invention, the dentifrice composition comprises between 1-80% by mass of the HP 101 microcrystalline cellulose binder, preferably 1-20% by mass, more preferably 1-15%, even more preferably between 1-10%. According to a specific configuration, the toothpaste composition contains 5% by weight of HP 101 microcrystalline cellulose.

[0070] The binder polyvinylpyrrolidone K30 (PVP K30) belongs to the group of polyvinylpyrrolidones, also referred to as PVP, PNVP; povidone; Betadine; CAS Number 9003-39-8. Said ingredient is a polymer soluble in polar solvents, including water, and is capable of stabilizing hydrogen bonds. According to the present invention, the binder polyvinylpyrrolidone K30 (PVP K30) added to the dentifrice composition also plays the role of film former, counterbalancing the wear of the tooth surface caused by the abrasives included in the composition, such as silica, especially amorphous silica. .

[0071] According to an embodiment of the present invention, the dentifrice composition comprises between 1-15% by mass of the binder polyvinylpyrrolidone K30 (PVP K30), preferably 3-10% by mass, more preferably 4-7%, even more preferably between 4.5-6%. According to a specific embodiment of the present invention, the solid dentifrice composition contains 5% by weight of polyvinylpyrrolidone K30 (PVP K30).

[0072] As in the case of the binders above, the other binders can perform additional functions. For example, xylitol is known to play a sweetener role in toothpaste formulations, as well as in several other dental and food products. In this sense, the identification of ingredients as binders is not done here in order to limit the ingredient to a certain function, it is just a way of describing them in an orderly way, in order to give greater clarity to the revealed matter.

Disintegrating Agents

[0073] Within the scope of the present invention the term “disintegrating agent” refers to any material that facilitates or accelerates the dissolution of a tablet. Examples of disintegrants include: cellulose derivatives, such as low-substituted hydroxypropylcellulose, carboxymethylcellulose, calcium carboxymethylcellulose and internally cross-linked sodium carboxymethylcellulose (croscarmellose sodium), microcrystalline cellulose, HP101 microcrystalline cellulose; cross-linked polyvinylpyrrolidone (crospovidone or copovidone); and chemically modified starches, such as carboxymethyl starch, sodium carboxymethyl starch, sodium starch glycolate and any mixture thereof.

[0074] The inclusion of disintegrating agents assists in breaking and dissolving the tablet once in the patient's mouth, promoting the release of the active ingredients and/or herbal agents and other components of the composition.

[0075] According to an embodiment of the present invention, the disintegrant used in the composition is chosen from the group consisting of: microcrystalline cellulose HP 101; polyvinylpyrrolidone (PVP), in particular polyvinylpyrrolidone K30 (PVP K30); and Hydroxypropylmethylcellulose.

[0076] According to a preferred embodiment of the present invention, the dentifrice composition comprises the disintegrating agent Hydroxypropylmethylcellulose. Still according to the same configuration, the composition comprises an amount between 1-10% by mass of Hydroxypropylmethylcellulose, preferably 1-8% by mass, more preferably 1-5%. According to a specific embodiment of the present invention, the solid dentifrice composition contains 2% by weight of Hydroxypropylmethylcellulose.

[0077] The ingredient Hydroxypropylmethylcellulose can also be named CAS number 9004-65-3. In addition to its use as a disintegrating agent, Hydroxypropylmethylcellulose can be used as a thickener.

Lubricants

[0078] Within the scope of the present invention the term "lubricant” refers to a material that can reduce the friction that arises at the interface of the tablet and the matrix wall during compression and ejection. Lubricants can also serve to prevent adhesion to the press and die wall. The term “nonstick” can also be used to refer specifically to substances that function during ejection. As used in the present patent application, however, the term "lubricant" is used generically and includes "nonsticks."

[0079] Lubricants can be intrinsic or extrinsic. A lubricant that is applied directly to the surface of the compression tool in the form of a film, such as by spraying into the die cavity and/or press surfaces, is known as an extrinsic lubricant. Their use requires complex application equipment and methods that add costs and reduce productivity. For this reason, a preferred embodiment of the present invention is the addition of at least one intrinsic lubricant. This class of lubricants is generally incorporated into the material before it is compressed. Suitable intrinsic lubricants for inclusion in the present dentifrice composition are: stearic acid, magnesium and calcium stearate, zinc stearate, hydrogenated and partially hydrogenated vegetable oils (e.g., peanut oil, cottonseed oil, sesame oil, olive oil , corn oil and theobroma oil, Sterotex), animal fats, glycerin, glycol, polyethylene glycol, polyoxyethylene monostearate, talc, light mineral oils, sodium benzoate, sodium lauryl sulfate or magnesium lauryl sulfate, magnesium oxide and the like, silica colloidal, such as Tixosil 43B; silicic acids such as silicic anhydride or silicate hydrate; waxes such as beeswax or spermaceti; Boric acid; adipic acid; fumaric acid; sodium stearyl fumarate; and D,L-leucine and any mixture thereof.

[0080] According to one embodiment of the invention, the dentifrice composition comprises at least one of the lubricants sodium benzoate or sodium lauryl sulfate.

[0081] The ingredient sodium benzoate can also be called by its CAS number 532-32-1. In addition to serving as a lubricant, sodium benzoate can also act as a preservative in the dentifrice composition of the present invention.

[0082] The ingredient sodium lauryl sulfate can also be called sodium lauryl sulfate, or by its CAS number 151-21-3. In addition to performing its function, sodium lauryl sulfate can act in the composition as a surfactant.

[0083] According to an embodiment of the present invention, the lubricant sodium benzoate is added to the composition in the amount of 0.1-10% by mass, preferably 0.1-8%, more preferably 0.1-2%. According to the specific configuration of the present invention, the composition contains 0.4% by weight of sodium benzoate.

[0084] In a preferred embodiment of the present invention, the tablet dentifrice composition comprises sodium lauryl sulfate in the amount of 0.5 and 5% by mass, preferably 0.5 to 3% by mass, more preferably 1 to 3%. In a specific configuration of the present invention, the surfactant is sodium lauryl sulfate in an amount of 3% by weight.

[0085] According to a preferred embodiment of the present invention, the dentifrice composition comprises sodium benzoate and sodium lauryl sulfate. Foaming agents

[0086] The present composition may also contain suitable foaming agents, such as those that are reasonably stable and form foam over a wide pH range. Foaming agents include nonionic, anionic, amphoteric, cationic, zwitterionic types, synthetic detergents, and mixtures thereof. Many suitable nonionic and amphoteric surfactants are disclosed in the prior art (see Patent 3,988,433; US Patent 4,051,234, among others).

[0087] The present composition optionally comprises a safe and effective amount of a foaming agent, in another configuration comprising from about 0.001% to about 20% by mass, in another configuration from about 0.05% to about 9%. and in yet another configuration from about 0.1% to about 5% by mass of the foaming agent composition. In one embodiment, the foaming agent is selected from the group consisting of cocam idopropyl betaine, sodium alkyl sulfate, poloxamer, PEG40 sorbitan isostearate and any mixtures thereof. Surfactants

[0088] The present dentifrice composition may further comprise a surfactant. Within the scope of the present invention, the term "surfactant" refers to substances that reduce surface tension or influence the contact surface between two liquids, being able to form micellar emulsions between hydrophilic and hydrophobic substances. Synonyms for "surfactant" are: "surfactant", “detergent”, “emulsifier”.

[0089] Surfactants can be categorized into 4 different classes, including cationic, anionic, non-ionic and amphoteric. Cationic surfactants are agents with at least one functional group that provide positively charged organic ions in aqueous solution. Typical examples are ammonium quaternaries. Anionic surfactants are those that have at least one functional group and that provide negatively charged organic ions when in aqueous solution. Non-ionic surfactants are those that have uncharged hydrophilic groups attached to the grease chain. Finally, amphoteric surfactants are those that contain both a flammable acid radical and a basic radical in their structure. When in aqueous solution, these compounds present anionic or cationic characteristics depending on the pH of the solution.

[0090] According to an embodiment of the present invention, the surfactant used in the composition is an anionic surfactant. Examples of ionic surfactants suitable for the composition of the present invention include the water-soluble salts of alkyl sulfates having 8 to 20 carbon atoms in the alkyl moiety (e.g., sodium alkyl sulfate) and the water-soluble salts of sulfonated monoglycerides of acids fatty having 8 to 20 carbon atoms; sodium lauryl sulfate and sodium coco monoglyceride sulfonates and any mixture thereof. Other suitable anionic surfactants are sarcosinates, such as sodium lauroyl sarcosinate, taurates, sodium laurylsulfoacetate, sodium lauroylsethionate, sodium laureth carboxylate and sodium dodecyl benzenesulfonate and any mixture thereof.

[0091] According to an embodiment of the present invention, surfactants suitable for the dentifrice composition include amphoteric surfactants in general and amphoteric betaine surfactants.

[0092] In a preferred embodiment of the present invention, the tablet dentifrice composition preferably comprises at least the surfactant sodium lauryl sulfate in the amount of 0.5 and 5% by mass, preferably 0.5 to 3% by mass, more preferably 1 to 3%. In a specific configuration of the present invention, the surfactant is sodium lauryl sulfate in an amount of 3% by weight. Sweeteners

[0093] Within the scope of the present invention, the term “sweeteners” refers to substances with low or no energy value that provide a sweet taste to a composition. Sweeteners are also called sweeteners. In addition to sucrose (the most common natural sugar worldwide), other widely used substances are saccharin, cyclamate and thaumatin. Sweeteners can be classified as natural, for example fructose, sorbitol, etc., which have fewer calories than the glucose present in sucrose, or artificial or synthetic, for example sodium saccharin, cyclamates, etc., which do not have caloric values. .

[0094] Sweetening agents that may optionally be used in the dentifrice composition disclosed in the present patent application include: sucralose, sucrose, glucose, saccharin, dextrose, levulose, lactose, mannitol, sorbitol, fructose, maltose, xylitol, saccharin salts , thaumatin, aspartame, D-tryptophan, dihydrochalcones, cyclamate salts, especially sodium cyclamate and sodium saccharin and mixtures thereof.

[0095] In one embodiment of the invention, the composition comprises from about 0.1% to about 10% by mass of sweeteners, in another configuration from about 0.1% to about 1% by mass.

[0096] According to the present embodiment of the invention, the composition comprises the sweeteners saccharin and/or xylitol.

[0097] The saccharin ingredient can also be designated by its commercial form sodium saccharin and by its CAS number 128-44-9. In addition to acting as a sweetener, saccharin can act as a flavoring agent.

[0098] According to an embodiment of the present invention, the dentifrice composition comprises saccharin in the amount of 0.1-2% by mass, preferably 0.1 -1.5% by mass, more preferably 0.1-1%, even more preferably between 0.1-0.5%. According to specific configurations of the present invention, the composition has 0.2 or 0.3% by weight of saccharin.

[0099] The ingredient xylitol can also be designated by its CAS number 87-99-0. In addition to its sweetening function, the ingredient xylitol can act as an anti-cavity agent, flavoring agent, among other functions.

[00100] According to an embodiment of the present invention, the dentifrice composition comprises xylitol in the amount of 0.1-15% by mass, preferably 0.1-10% by mass, more preferably 2-8%. According to the specific configuration of the present invention, the composition has 5% by weight of xylitol. Flavorings

[00101] Within the scope of the present invention, the term "flavorings" refers to substances capable of imparting specific odors or flavors to a composition. The term "flavorings" comprises substances called flavorings (responsible for imparting aromas) and flavorings (responsible for imparting flavor).

[00102] In one embodiment of the present invention, the tablet dentifrice composition comprises at least one flavoring selected from a group comprising: sodium saccharin and aspartame; acidic flavorings such as citric acid, malic acid and tartaric acid; mint flavors, such as menthol, peppermint and spearmint, lemon and orange, eucalyptol or mixtures thereof.

[00103] The ingredient eucalyptol can also be referred to by its CAS number 470-82-6. In addition to acting as a flavoring, eucalyptus can act as an active ingredient in the composition of the present invention.

[00104] According to an embodiment of the present invention, the dentifrice composition comprises mint flavor in an amount of 0.15% by mass, preferably 0.5-3% by mass, more preferably 0.75-1.25% . According to one embodiment of the present invention, the dentifrice composition has 1% by weight of mint flavor.

[00105] According to an embodiment of the present invention, the dentifrice composition comprises eucalyptus in the amount of 0.01-5% by mass, preferably 0.01-3% by mass, more preferably 0.05-3%. According to one embodiment of the present invention, the composition has 1% by weight of eucalyptol.

[00106] According to the present embodiment of the invention, the composition comprises mint and eucalyptol aroma. Preservatives

[00107] Within the scope of the present invention, the term "preservatives" refers to substances added to a composition with the purpose of delaying or preventing changes caused by microorganisms or enzymes.

[00108] In one embodiment of the present invention, the tablet toothpaste composition preferably comprises at least one preservative chosen from a group comprising: sodium benzoate, salicylic acid, methylparaben, propylparaben, benzalkonium chloride and amphoteric acid and any mixture thereof.

[00109] According to the embodiment of the invention, the dentifrice composition comprises the preservative sodium benzoate.

[00110] According to an embodiment of the present invention, the dentifrice composition comprises sodium benzoate in the amount of 0.1-2% by weight, preferably 0.1 -1.5%, more preferably 0.1-1%. According to the specific configuration of the present invention, the composition contains 0.4% by weight of sodium benzoate. Active principle

[00111] Within the scope of the present invention, the term "active ingredient" refers to substances comprising anticariogenic, antitartar, anticalculus, anti-inflammatory, soft tissue regeneration, promotion of remineralization, reduction of demineralization and healing activities or any combination of these.

[00112] In one embodiment of the present invention, the tablet dentifrice composition comprises at least one active ingredient chosen from a group comprising: hyaluronic acid, sodium monofluorophosphate, dimethylsilanediol salicylate (DSBC), source of fluoride ions (such as, sodium fluoride and sodium monofluorophosphate), xylitol, pyrophosphate, including tetrasodium pyrophosphate and sodium acid pyrophosphate.

[00113] According to an embodiment of the present invention, the dentifrice composition comprises hyaluronic acid in the amount of 0.0110% by mass, preferably 0.01-8% by mass, more preferably 0.01-5%, even more preferably 0.01-2%. According to one embodiment of the present invention, the dentifrice composition has 0.2% by weight of hyaluronic acid.

[00114] According to an embodiment of the present invention, the dentifrice composition comprises sodium monofluorophosphate in the amount of 0.01-3% by mass, preferably 0.01-2% by mass, more preferably 0.01-1, 5%. According to one embodiment of the present invention, the dentifrice composition has 1.14% by weight of sodium monofluorophosphate.

[00115] According to an embodiment of the present invention, the dentifrice composition comprises dimethylsilanediol salicylate (DSBC) in the amount of 0.01-5% by mass, preferably 0.01-3% by mass, more preferably 0.01 -2%, even more preferably 0.01-1% by mass. According to embodiments of the present invention, the dentifrice composition has 0.05% or 0.1% by weight of dimethylsilanediol salicylate (DSBC).

[00116] According to an embodiment of the present invention, the dentifrice composition comprises xylitol in the amount of 1 -15% by mass, preferably 1-10% by mass, more preferably 2-7%. According to the specific configuration of the present invention, the composition has 5% by weight of xylitol.

[00117] According to an embodiment of the present invention, the dentifrice composition comprises tetrasodium pyrophosphate in the amount of 0.05-2.5% by mass, preferably 0.05-2% by mass, more preferably 0.1-1 %. According to one embodiment of the present invention, the dentifrice composition has 0.5% by mass of tetrasodium pyrophosphate. Fluoride ion source

[00118] The fluoride ion source provides free fluoride ions during chewing of the composition. In one embodiment, the active oral care ingredient is a source of fluoride ions selected from the group consisting of sodium fluoride, tin fluoride, indium fluoride, organic fluorides such as amine fluorides and sodium monofluorophosphate. Preferably, the composition of the present invention comprises sodium monofluorophosphate.

[00119] The ingredient sodium monofluorophosphate can also be designated as sodium fluorophosphate or by its CAS number 10163-15-2.

[00120] According to an embodiment of the present invention, the dentifrice composition comprises sodium monofluorophosphate in the amount of 0.5-3% by mass, preferably 0.5-2% by mass, more preferably 0.51.5%. According to one embodiment of the present invention, the dentifrice composition has 1.14% by weight of sodium monofluorophosphate.

[00121] Sodium monofluorophosphate is considered an important anti-caries agent. Other optional anti-caries agents include agents that remineralize enamel and dentin. These remineralization agents prevent, treat and/or reverse the cavity process. Optional remineralizing agents are selected from the group consisting of a source of calcium ions that is soluble in saliva or becomes soluble with increased heat or changes in pH and/or a source of phosphate ions; complexes of a fluoride ion source with an insoluble or soluble calcium ion source and their amorphous forms; complexes of a fluoride ion source with an insoluble or soluble phosphate ion source and their amorphous forms; fluoride ion source with a calcium ion and insoluble or soluble phosphate source and its amorphous forms, amorphous forms, dicalcium phosphate, hydroxapatite; nanohydroxyapatite; a combination of strontium EDTA complex and a soluble fluoride ion source; casein glycomacropeptide and mixtures thereof.

[00122] According to an embodiment of the present invention, the anti-caries agents of the dentifrice composition can be adjusted to suit patients with implants and/or who require regeneration and other care in relation to oral soft tissues. In these cases, the source of fluoride or fluoride ions has its effectiveness and relevance of use reduced, as the implants are not susceptible to cavities and do not present direct benefits for scar repairs and soft tissue health. On the other hand, the absence of fluoride can increase the risk of cavities in the implant patient's other natural teeth. To counterbalance this risk, the composition of the toothpaste may include an active ingredient of the polysaccharide type with anticariogenic action, xylitol, to supplant the activity of fluoride.

[00123] Another case in which fluoride can be advantageously replaced by xylitol is in the treatment of patients with implants or restorations containing titanium. In these cases, fluoride attacks the surface of the titanium present in the implants, which can lead to quantitative and qualitative changes that have negative potential for the peri-implant mucosa and bone structure. Hyaluronic acid

[00124] According to the preferred configuration of the present invention, the composition can be added with hyaluronic acid to promote the stimulation of repair processes associated with combating inflammation. This ingredient is a component of connective tissue initially used for procedures to fill defects in dermal papilla, that is, its use belonged to a completely different technological field. The present invention pioneers the use of this ingredient in a solid dentifrice formulation, applying hyaluronic acid for the treatment of inflammatory conditions and for healing and repair during the treatment of periodontal disease and in the treatment of ulcers in the oral cavity. In this sense, the present invention extracts all the benefits of hyaluronic acid, in particular its bacteriostatic, anti-inflammatory, antioxidant and mucosal regenerating effects, and applies them in a distinct technological field, that of Dentistry. It is clear that the transport of technical knowledge between such different areas is not obvious in nature, being proof of the inventive activity of the present invention. In addition to the uses mentioned, hyaluronic acid can be used in the composition of the present invention as a humectant.

[00125] The ingredient hyaluronic acid can also be designated by its CAS number 9004-61-9.

[00126] As shown in the examples, the inventors found experimentally that the application of hyaluronic acid to human fibroblasts significantly increased the gene expression of the proteins Fibroblast Growth Factor Receptor 1 (FGFR1), Cyclin Dependent Kinase 2 (CDK2) and Vascular Endothelial Growth Factor (VEGF), indicating increased proliferation of endothelial cells and regeneration of soft tissues and the process of angiogenesis.

[00127] According to an embodiment of the present invention, the dentifrice composition comprises hyaluronic acid in the amount of 0.01-10% by mass, preferably 0.01-8% by mass, more preferably 0.01-5%, even more preferably 0.01-2%. According to one embodiment of the present invention, the dentifrice composition has 0.2% by weight of hyaluronic acid.

[00128] Furthermore, the use of hyaluronic acid in combination with the herbal agent green tea extract (Cammelia sinensis) results in an unexpected synergistic effect, further confirming the inventive nature of the present invention. Details regarding the verification of the synergistic effect are presented in greater detail later in the Examples of the specification Dimethylsilanediol salicylate (DSBC)

[00129] The active ingredient dimethylsilanediol salicylate (DSBC) acts on the regeneration of gingival tissue significantly, accelerating the healing or regeneration process, in addition to acting on remineralization in teeth, prevention of bone atrophy, anti-inflammatory action and cell renewal.

[00130] DSBC can be designated by its chemical name silanediol salicylate (silanediol salicylate). It is an organic silicon used in oral hygiene products with properties on the mucosa: regenerating, anti-inflammatory and cell renewal action.

[00131] The addition of DSBC to the composition of the present invention results from the verification of a synergistic effect between it and the surfactant sodium lauryl sulfate (LSS). DSBC nullifies the side effect of peeling of the oral mucosa generated by sodium lauryl sulfate (LSS) when used in high concentrations.

[00132] According to an embodiment of the present invention, the dentifrice composition comprises dimethylsilanediol salicylate (DSBC) in the amount of 0.01-5% by mass, preferably 0.01-3% by mass, more preferably 0.01- 3%, even more preferably 0.01-2% by mass. According to embodiments of the present invention, the dentifrice composition has 0.05% or 0.1% by weight of dimethylsilanediol salicylate (DSBC). Tetrasodium pyrophosphate

[00133] The ingredient tetrasodium pyrophosphate has anti-tartar as one of its main functions. Alternatively, this ingredient can also be used to stabilize and buffer the pH of the composition, especially in relation to salivary pH.

[00134] Tartar or dental calculus, formed from the calcification of a thick biofilm, is most commonly located near the exit of the salivary gland ducts, mainly on the lingual surface of the lower incisors and upper molars and components of salivary origin are found there. , microbial, blood and diet. In the formulations of our products, tetrasodium pyrophosphate was used as an anti-tartar agent, which has the function of blocking the sites available for crystal growth and compromising their maturation, preventing the formation of dental calculus.

[00135] The ingredient can also be designated by its CAS number7722-88-5.

[00136] According to an embodiment of the present invention, the dentifrice composition comprises tetrasodium pyrophosphate in the amount of 0.05-2.5% by mass, preferably 0.05-2% by mass, more preferably 0.1-1 %. According to one embodiment of the present invention, the dentifrice composition has 0.5% by mass of tetrasodium pyrophosphate. Sodium Acid Pyrophosphate

[00137] The ingredient sodium acid pyrophosphate can be added to help maintain the individual's oral health. Furthermore, this ingredient can act to stabilize and buffer the pH of the composition, particularly in relation to salivary pH.

[00138] The ingredient sodium acid pyrophosphate can also be designated as disodium pyrophosphate or by CAS number 7758-16-9.

[00139] According to an embodiment of the present invention, the dentifrice composition comprises sodium acid pyrophosphate in the amount of 0.011% by mass, preferably 0.05-0.8% by mass, more preferably 0.01 -0.5 %, even more preferably 0.01 -0.3%. According to one embodiment of the present invention, the dentifrice composition has 0.15% by weight of sodium acid pyrophosphate.

[00140] Chelating agents are intended to sequester metal ions from a formulation or this formulation in solution. According to one embodiment of the present invention, a chelating agent suitable for use in the dentifrice composition is EDTA, also known as ethylene diamine tetraacetic acid, disodium EDTA, disodium edetate or by its CAS number 139-33-3.

[00141] According to an embodiment of the present invention, the dentifrice composition comprises EDTA in the amount of 0.01-1% by mass, preferably 0.01-0.5% by mass, more preferably 0.01-0.1 %. According to one embodiment of the present invention, the dentifrice composition has 0.05% by weight of EDTA. Buffering agents

[00142] Buffers function to stabilize the pH of the composition when in solution. Within the scope of the present invention, the main purpose of the buffering agent is to stabilize the pH of the composition in relation to changes in salivary pH.

[00143] According to one embodiment of the present invention, a suitable buffering agent is chosen from a group comprising: sodium acid pyrophosphate, tetrasodium pyrophosphate, sodium bicarbonate, sodium carbonate, citric acid, sodium citrate, potassium carbonate, sodium oxide, magnesium.

[00144] According to an embodiment of the present invention, the dentifrice composition comprises tetrasodium pyrophosphate in the amount of 0.05-2.5% by mass, preferably 0.05-2% by mass, more preferably 0.1-1 %. According to one embodiment of the present invention, the dentifrice composition has 0.5% by mass of tetrasodium pyrophosphate.

[00145] According to an embodiment of the present invention, the dentifrice composition comprises sodium acid pyrophosphate in the amount of 0.01 - 1% by mass, preferably 0.05- 0.8% by mass, more preferably 0.01 -0.5%, even more preferably 0.01 -0.3%. According to one embodiment of the present invention, the dentifrice composition has 0.15% by weight of sodium acid pyrophosphate.

[00146] Within the scope of the present invention, "phytotherapeutic agents” are those substances or extracts originating from plants capable of performing therapeutic functions. For the present invention, the following are desirable therapeutic functions for phytotherapeutic agents: anti-inflammatory; anti-edematous , prevention or control of gingivitis; bactericide; antioxidant, anti-caries, antitartar, soft tissue regeneration, stimulation of cell proliferation, reduction of biofilm formation; and antiseptics.

[00147] Phytotherapeutic agents may consist of plant extracts made by mechanical methods, having an oily or aqueous appearance. Furthermore, such herbal agents may consist of essential oils produced from raw vegetable materials. Such essential oils are also called volatile or ethereal oils, and are predominantly obtained through distillation, compression, solvent extraction or resination techniques. Alternatively, phytotherapeutic agents can be presented in the form of glycolic extracts from raw plant materials.

[00148] According to an embodiment of the present invention, the herbal agent(s) are chosen from a group comprising: green tea extract (Cammelia sinensis), tea tree extract (Melaleuca Alternofilia), Menta piperita, pomegranate extract (Punica granatum), guaçatonga extract (Casearia sylvestris) and green propolis extract (Baccharis dracunculifolia).

[00149] The ingredient green tea extract (Cammelia sinensis) can also be designated by its CAS number 84650-60-2.

[00150] The ingredient tea tree extract (Melaleuca Alternofilia) can also be designated as tea tree glycolic extract (Melaleuca Alternofilia), tea tree extract, melaleuca glycolic extract or by its CAS number 85085-48-9.

[00151] According to an embodiment of the present invention, the dentifrice composition comprises green tea extract (Cammelia sinensis) in the amount of 0.1-10% by mass, preferably 0.1-8% by mass, more preferably 0. 1-7% by mass, more preferably 0.1-5%, even more preferably 0.1-1%. According to one embodiment of the present invention, the dentifrice composition has 0.5% by weight of green tea extract (Cammelia sinensis) extract.

[00152] According to an embodiment of the present invention, the dentifrice composition comprises tea tree extract (Melaleuca Alternofilia) in the amount of 0.01-10% by mass, preferably 0.01-8% by mass, more preferably 0. 01-5% by mass, more preferably 0.01-3%, even more preferably 0.01-2%. According to one embodiment of the present invention, the dentifrice composition has 0.1% by weight of tea tree extract (Melaleuca Alternofilia).

[00153] According to an embodiment of the present invention, the dentifrice composition comprises Green Propolis (Baccharis dracunculifolia) in the amount of 0.01-5% by mass, preferably 0.01-3% by mass, more preferably 0.01- 0.4%.

[00154] According to a preferred embodiment of the present invention, the dentifrice composition comprises both herbal agents tea tree extract (Melaleuca Alternofilia) and green tea extract (Cammelia sinensis). pH of the composition

[00155] Another important factor for balancing the demineralization and remineralization process, as well as for scar repair and oral soft tissue health, is the hydrogen potential (pH), as these processes are influenced in their results if the oral environment is found. if very acidic or basic.

[00156] According to an embodiment of the present invention, the dentifrice composition has, when in solution, a pH of 6-10, preferably 7-9, more preferably 7-8. Additional Considerations

[00157] As disclosed throughout this patent application, there are several ingredients in the solid dentifrice composition capable of performing more than one function. Such functions are performed simultaneously, however, the adjustment in the concentration of multifunctional ingredients must be adjusted for specific applications in order to optimize their functions. Said concentration adjustment can be made by a person skilled in the art without incurring undue experimentation. Therefore, the present invention should not be interpreted strictly within the limits provided by the present specification. In this sense, the examples provided below should not be taken as limiting configurations, but as non-limiting illustrative configurations of the present invention.

[00158] In addition to the formulations and compositions disclosed in the present patent application, the invention also refers to the production process resulting in the composition of a solid dentifrice. The details of the stages of the production process are revealed in the examples section of the descriptive report. EXAMPLES Example 1 - Assessment of synergistic effects between hyaluronic acid and green tea extract

[00159] 1.1 Motivation

[00160] Soft tissue regeneration and maintenance has been placed at the center of periodontology and oral health care. Here, the purpose of this study was to better evaluate the role of hyaluronic acid and green tea, as well as their synergism, in fibroblasts, seeking to understand their role in central genes related to cell growth and survival.

[00161] 1.2 Experimental design

[00162] To evaluate the existence of a synergistic effect, an experimental design was determined as illustrated in Fig. 1. To evaluate whether the solutions influence the fibroblastic phenotype, human fibroblasts were cultivated in a CO2 incubator (a) and subsequently subjected to a range of concentrations of hyaluronic acid or green tea extract (b) to determine their cytotoxicity by performing the MTT assay (c). Samples were also collected to later evaluate gene expression by performing qPCR analysis (d).

[00163] 1.3 Data and statistics

[00164] To evaluate the molecular changes promoted by hyaluronic acid or green tea, we subjected human fibroblasts to cell culture medium supplemented with 10% of each solution (v/v), in addition to considering a synergism between them. To evaluate synergism, we previously prepared the solution considering 10% hyaluronic acid and 10% green tea. Suitably, fibroblasts challenged for up to 24 hours were harvested and biological samples collected to allow molecular analysis using qPCR technology (QuantStudio™ 3 Real-Time PCR System, Thermo Fisher, USA). Genes related to fibroblast survival and growth (AKT, CDKs), as well as fibroblast phenotype (FGF23, FGFR2) and angiogenesis stimulation (VEGF) were evaluated, as follows:

[00165] 1.3.1 AKT expression analysis

[00166] Fig.2 below shows the effect of these treatments considering the expression of the AKT gene. AKT proteins therefore regulate a wide variety of cellular functions, including cell proliferation, survival, metabolism and angiogenesis in eukaryotic cells (Manning & Toker, 2017), and why this AKT is considered an important biomarker to know the effect of different substances candidates for application in human health. Here, our data show that, although there are significant differences in both molecules being considered unique, the effect of synergism had a greater influence on AKT gene expression - being more than 100-fold changes compared to the control. Importantly, a complete statistical analysis of AKT expression is presented in Table 1.

[00167] As illustrated in Fig 2. AKT, an important biomarker of cell survival, was evaluated in response to the synergism between hyaluronic acid (10%) and green tea (10%) in fibroblasts. Control cultures were considered when cells were maintained under classical conditions, without any treatment. The expression value was normalized with 18S (housekeeping gene) data.

[00168] 1.3.2. Cell cycle analysis: CDK expression

[00169] As AKT is related to cell survival and proliferation (Manning & Toker, 2017) and was greater considering the synergism between hyaluronic acid (10%) and green tea (10%), we decided to further explore this effect in fibroblasts evaluating genes related to cell cycle proliferation; therefore, the CDK2, CDK4 and CDK6 genes were evaluated (Patterson et al., 2021). Importantly, our data show significant and greater changes in all cell cycle genes evaluated when the two solutions were tested together (synergism) (Fig.3). These are very welcome data, as during tissue recovery and regeneration, cell growth needs to be considered. Tables 2-4 show the statistical analysis of CDK expressions.

[00170] As shown in Fig.3, genes related to cell growth were affected by the synergism between hyaluronic acid (10%) and green tea (10%) in fibroblasts. Control cultures were considered when cells were maintained under classical conditions without any treatment. The expression value was normalized with 18S (housekeeping gene) data. CDK: Cyclin-Dependent Kinase.

[00171] 1.3.3. VEGF expression analysis

[00172] As shown, AKT appears to be an important hub for driving the molecular changes promoted by the synergism between hyaluronic acid (10%) and green tea (10%) in fibroblasts. Here, we further explored whether this effect promotes some changes in the VEGF gene, strongly related to angiogenesis processes. Note that during tissue regeneration, angiogenesis is the most efficient way to create new blood vessels to supply physiological needs, such as nutrients and oxygen, for cellular functions (Li et al., 2005).

[00173] Our data show that the synergism between hyaluronic acid (10%) and green tea (10%) promoted greater expression of the VEGF gene (change greater than 10 times than the control) (Fig.4). It is noteworthy that Table 5 shows the statistical analysis of VEGF expression.

[00174] As illustrated in Fig.4, VEGF, an important growth factor for driving angiogenesis, was higher in response to the synergism between hyaluronic acid (10%) and green tea (10%) in fibroblasts. Control cultures were considered when cells were maintained under classical conditions without any treatment. The expression value was normalized with 18S (housekeeping gene) data. VEGF: Vascular Endothelial Growth Factor.

[00175] 1.3.4. Analysis of FGF23 and FGFR2 expressions

[00176] Growth factors are potential agents to achieve specific tissue regeneration, as they broadly regulate biological functions in cellular functions, mainly affecting proliferation, migration and differentiation in soft connective tissues. Recently, several studies have implicated the in vitro biological functions of FGFs for tissue regeneration (Yun et al., 2010). Therefore, we investigated the effect of synergism between hyaluronic acid (10%) and green tea (10%) in modifying the expression of the FGF23 and FGFR2 genes in vitro.

[00177] Our data show that both genes were expressed considering the synergism between the solutions; achieved more than 30-fold changes for FGFR2 and more than 10-fold changes for FGF23 (Fig.5). Tables 6.7 show the statistical analysis of the expression of FGF23 and FGFR2.

[00178] As illustrated in Fig.5, the FGF23 and FGFR2 genes were overexpressed in response to the synergism between hyaluronic acid (10%) and green tea (10%) in fibroblasts. Control cultures were considered when cells were maintained under classical conditions without any treatment. The expression value was normalized with 18S (housekeeping gene) data. FGF23: Fibroblast growth factor 23 and its receptor, FGFR2.

[00179] 1.4 Conclusion

[00180] Taken together, this study clearly shows that the synergism between hyaluronic acid (10%) and green tea (10%) affects the fibroblast phenotype, promoting better performance of genes related to soft tissue regeneration and requiring growth signaling cellular and angiogenesis stimulus, as suggested and represented in Fig.6.

[00181] As illustrated in Fig. 6, the main findings found in this study were: the conjunction of signaling promoted by synergism led to the activation of AKT as a hub to conduct cellular events related to cell growth, survival and stimulation of angiogenesis. Taken into consideration, this signaling pathway is related to the regeneration of connective tissue, and the fibroblast is a fundamental cell in this scenario.

[00182] This synergistic effect has not yet been described by the state of the art, nor is there any publicly disclosed teaching that would encourage a person skilled in the art to predict or use such an advantageous synergistic effect for the preparation of a solid dentifrice. Example 2 - Production process for obtaining solid toothpaste composition in tablet form

[00183] To obtain and maintain its physical stability, it is important to follow the sequence:

[00184] Phase I: Weigh the necessary quantities of solid components, with the smallest quantity in the formulation, sieve through a mesh with a nominal pore opening of 0.5mm and mix Tetrasodium Pyrophosphate, Saccharin, Sodium Ethylene Diaminetetraacetic Acid (EDTA), Acid Pyrophosphate sodium, Sodium monofluorophosphate (Optional).

[00185] Phase II: Weigh the following components: Microcrystalline cellulose, HPMC, Sodium lauryl sulfate, Xylitol, Thixosil 43B, CaCO3.

[00186] Phase III: Sieve the components from phase II and combine with those from phase I and mix for one hour in a V-type mixer. (Solid/solid mixture)

[00187] Phase IV: preparation of the binding solution; dissolve the components of the binder solution in water, whose water mass is equivalent to 25% of the total mass of solids in the formulation. Polyvinylpyrrolidone K30, Hyaluronic Acid, Green Tea Extract.

[00188] Phase V: obtaining the wet mass to be granulated: Place the powder mixture obtained in phase III in a mixing bowl and with it moving, add the binder solution little by little until a cohesive mass is formed. This solid/liquid mixing process lasts between 40 and 60 minutes to obtain a homogeneous mass, without free water.

[00189] Phase V: granulation and drying process: The mass obtained in phase V must be granulated in a mesh with a nominal pore opening of 2.0 mm and placed in an oven at a temperature of 45°C to dry, until a maximum humidity of 3%. The dried granules must be returned to the granulator and passed through a mesh with a nominal pore opening of 1mm (dry granulated)

[00190] Phase VII: addition of external components: liquid components with a low vaporization point, dimethylsilanediol salicylate (DSBC), mint flavor, eucalyptol, melaneuca glycolic extract must be incorporated into the following components, in the following order: Cellulose (10 % of the total mass of cellulose in the formulation), CaC03 (7% of the total mass of CaC03 in the formulation), Tixosil (20% of the total mass of Tixosil in the formulation), this incorporation must be done in a mortar with the help of a pestle.

[00191] Phase VIII: after incorporation, the external parts must be sieved in sieves with a nominal pore opening of 0.5mm and added to the dry granulate and mixed for 60 minutes in a V-type mixer. Granule ready to be subjected to compression.

[00192] Compaction can be carried out in eccentric or rotary compaction machines, using a concave punch and a 12 mm diameter matrix, and a mass of 650 mg, and with mechanical resistance to breaking when applied force between 4 and 6 kgf. Friability less than 1%. Example 3 - Solid toothpaste tablet formulation

[00193] According to one embodiment of the present invention, the dentifrice composition can be easily adapted to meet different needs. The formulations below show a formulation for the treatment of patients with implants, being suitable both for the maintenance and prolongation of the implant's life and for recoveries after implant installation, and another formulation intended for patients seeking cosmetic treatment, mainly, but not only , maintaining and prolonging the surface shine of dental enamel and restorative materials.

[00194] The two compositions differ in that: the formulation for cosmetic purposes contains sodium monofluorophosphate, while for patients with implants it does not contain it due to the possibility of fluorine reacting with the metal of the implant. Quantitative differences between the two: Dimethylsilanediol Salicylate (cosmetic 0.1% and implants 0.05%), Saccharin (Cosmetic 0.3% and Implants 0.2%).

[00195] The technique and phases for producing the two compositions are the same, as small changes do not alter the processes.

[00196] Regarding the tablet formation process (granulation), the first attempt was the direct compression of the mixture of all the constituents of the formulation. Due to the composition having an angle of repose around 60° and a low apparent density, 0.3g/cm3. An angle of repose of 60o implies poor flow, that is, the composition does not have sufficient free flow for uniform and repetitive filling of the compaction matrix. With a density of 0.3g/cm3, a matrix with a nominal volume of at least 2.2 cm3 would be required, resulting in tablets with non-uniform mass and hardness.

[00197] Starting from the formulation in Table 10 of the product, the inventors sought to optimize the concentration of the ingredients to obtain an ideal formulation, combining better physical properties and effectiveness in its role in oral/dental hygiene and treatment.

[00198] Based on the information and results of the granulation results of the formulations in Tables 8 and 9, it was decided to apply a composition densification strategy using the wet granulation technique, using polyvinyl pyrrolidone (KVP K30), present in the composition to prepare the granulation liquid. After the granulation process, as already described, we obtained a granulate with good flow characteristics, an angle of repose of around 30° and a density of around 0.8g/cm3. In the compression test, we verified perfect filling of the matrix and tablets with uniform mass. However, even working with the compression machine at the limit of force application, there was no consolidation of the compacted material, that is, a tablet with low hardness and high friability.

[00199] In view of this, we chose to add to the composition the pharmacotechnical adjuvants, Microcrystalline Cellulose (7%) and Sodium Starch Glycolate (8%) maintaining the amount of Polyvinylpyrrolodone K30 (PVP K30, 5%) present in the formulation and the process wet granulation. In order not to change the quantity of most components, mass compensation by the addition of microcrystalline cellulose and sodium starch glycolate was made by the corresponding reduction of the majority component, calcium carbonate.

[00200] The resulting formulations are shown in Tables 11 and 12 below.

[00201] Maintaining the processes, this composition provided tablets with the desired quality and excellent sensation in the mouth. However, a new change in composition was necessary due to the difficulty in acquiring sodium starch glycolate on the national market. So we replaced sodium starch glycolate with hydroxypropylmethycellulose. Table 12. Solid dentifrice formulation aimed at patients with implants.

[00202] Maintaining the processes, this composition provided tablets with physical quality, however in the wet granulation process, the mass became very elastic, making the granulation process difficult due to the strong polymer/polymer interaction and other polymer components. Reflecting on the hardness of the tablet, even when compressing with minimum force to consolidate the compacted system.

[00203] This difficulty was eliminated by reducing the percentage of hydroxypropylmethycellulose from 8 to 2%. Example 5 - Preferred formulations

[00204] According to the preferred configuration of the present invention, the composition of the tablet dentifrice is that illustrated in Table 13, for application to patients with dental implants, and that illustrated in Table 14, for patients for cosmetic use.

Claims (14)

Oral dentifrice composition in tablet format comprising: a) at least one carrier; b) at least one surfactant; c) at least one abrasive; characterized by the fact that it comprises at least one active ingredient and at least one herbal agent. Composition according to claim 1, characterized by the fact that the carrier is a binder, which is chosen from a set comprising: polyvinylpyrrolidone (PVP); lactose; sucrose; dextrose; mannitol; sorbitol; xylitol; erythritol; lactitol; isomalt; maltitol; trehalose; tegatosis; calcium sulfate; bibasic calcium phosphate; tricalcium phosphate; tribasic calcium sulfate; starch, such as corn starch, potato starch, hydrogenated starch hydrolysates and sodium starch glycolate; calcium carbonate; cellulose; modified cellulose, such as microcrystalline cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and hydroxypropylethylcellulose; and their respective mixtures. Composition according to claim 2, characterized by the fact that it comprises hydroxypropylmethylcellulose in an amount of 1-10% by mass. Composition according to claim 2, characterized by the fact that it comprises microcrystalline cellulose in an amount of 1-80% by mass. Composition according to any of the previous claims characterized by the fact that the surfactant is chosen as being at least one of the set comprising: sodium lauryl sulfate, lauryl glucoside, amphoteric surfactants in general and amphoteric betaine surfactants. Composition according to any one of the previous claims characterized by the fact that it additionally comprises at least one carrier, this being a lubricant chosen from the set comprising: stearic acid; magnesium and calcium stearate; zinc stearate; hydrogenated and partially hydrogenated vegetable oils (e.g.; peanut oil; castor oil; cottonseed oil; sesame oil; olive oil; corn oil and theobroma oil; Sterotex); animal fats; glycerin; polyethylene glycol; polyoxyethylene monostearate; baby powder; light mineral oils; sodium benzoate; Sodium lauryl sulfate; magnesium oxide and the like and mixtures thereof. Composition according to any one of the preceding claims, characterized by the fact that the abrasive is chosen as being at least one of the set comprising: silicas, including gels, precipitates and amorphous silicas; insoluble sodium polymetaphosphate; hydrated alumina; aluminum hydroxide; aluminum oxide; calcium carbonate; calcium chlorophosphate dihydrate; calcium pyrophosphate; dicalcium phosphate, tricalcium phosphate; calcium polymetaphosphate; boron; sodium and calcium phosphosilicate; emery; grenade; glycine; perlite; pumice stone; Silicon carbide; sodium bicarbonate; zirconium oxide and zirconium silicate and two respective mixtures. Composition according to claim 7, characterized by the fact that it has an abrasiveness degree of 20 to 150 on the Relative Dentin Abrasivity (RDA) scale. Composition according to any of the above claims, characterized by the fact that it comprises the active ingredient hyaluronic acid. Composition according to any of the above claims, characterized by the fact that it comprises the active ingredient dimethylsilanediol salicylate (DSBC). Composition according to any of the previous claims, characterized by the fact that the herbal agent is green tea extract (Cammelia sinensis). Composition according to any of the previous claims, characterized by the fact that the herbal agent tea tree extract (Melaleuca Alternofilia). Composition according to claim 11, characterized by the fact that it contains an amount between 0.1% and 10% of the herbal agent green tea extract (Cammelia sinensis). Composition according to claim 12, characterized by the fact that it has an amount between 0.01% and 10% of the herbal agent tea tree extract (Melaleuca Alternofilia).

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