Process for Obtaining the Product for Prevention, Interruption of Dental Caries Lesions and Teeth Remineralization and Obtained Product

Abstract

Addresses the invention of product comprising: metal particles and/or free or complexed metal ions; fluoride; organic acid and polysaccharides, with or without additives, designed to prevent the occurrence of tooth lesions caused by dental caries, interrupt the development of such lesions, and to promote the remineralization of the affected teeth and a process of obtaining this product.

Claims

1. PRODUCT FOR PREVENTION, INTERRUPTION OF CARIOUS LESION AND REMINERALIZATION OF TEETH characterized by comprehending the following components: 0.001% to 0.50% in metal particles selected among silver, gold, copper, gold/silver alloys and gold/copper alloys, present several morphologies such as spherical, elliptical, prisms, rods and plates, with dimension values ranging from 1 nm to 500 nm, are obtained from precursor compounds of metals through controlled reduction reactions, where the precursor compounds are selected among oxides, acetates, nitrates, acetyl acetonates, carbonate, chloride, citrate, fluoride, iodate, lactate, iodide, nitrite, perchlorate, phosphate, sulfate and trifluoroacetate; 0.03% to 6.0% of a polysaccharide chitosan with molar mass ranging between 20 kDa and 10,000 kDa, its derivatives, which are selected among: carboxymethyl chitosan, chitosan lactate, acetate chitosan, amylopectin, amylose, alginates, alginic acid, pectin, xylan, and chitin, other biopolymers selected from: methyl cellulose, carboxymethyl cellulose, cellulose acetate, hydroxyethyl cellulose and hydroxypropyl cellulose, and, additionally, salts deriving from alginic acid sodium, potassium or calcium; 0.05% to 2.0% of a fluoride salt, which tends to be associated with cationic sites of the polysaccharide obtained from water-soluble salts, from aqueous solutions with an acidic pH up to a maximum value of 6.0 in both stock solutions; 0.05% to 4.0% of an organic acid selected among lactic acid, acetic acid, citric acid, oxalic acid, ascorbic acid and other organic acids of general RCOOH structure, where R refers to an organic radical; 0.01% to 2.0% of a liquid dispersing agent based on water, with a slightly acid pH eventually increased with co-solvent, which is chosen among glycols such as propylene glycol, poly (ethylene glycol), including different molar masses, substituted glycols, co-solvents such as ethanol, isopropanol and polysorbates and other polymeric additives for controlling the viscosity derived from cellulose as hydroxy-propyl, methyl cellulose, hydroxy-propyl cellulose, carboxy methyl cellulose and methyl cellulose; 0.01% to 10% of a flavoring chosen among: peppermint, mint, cinnamon, eucalyptus, cherry, strawberry and red berries.

2. PRODUCT FOR PREVENTION, INTERRUPTION OF CARIOUS LESION AND TEETH REMINERALIZATION according to claim 1, characterized by the metal particle being preferably silver, and the stoichiometric ratio of metal ion to reducing agent ranges from 0.10 to 10.0.

3. PRODUCT FOR PREVENTION, INTERRUPTION OF CARIOUS LESION AND TEETH REMINERALIZATION according to claim 1, characterized by the different forms of the product with its individual component options including the addition of medium or long chain polysaccharides that perform the following functions: antibacterial activity; increased physical and chemical stability for the compositions, which results in an increased expiration time for products; stabilization of the nanoparticles resulting from interactions between the surface of the particles and functional groups and/or loads located in the structure of polysaccharides; ionic association with ions present in the composition and the ability to obtain compositions with higher concentration of active principle.

4. PRODUCT FOR PREVENTION, INTERRUPTION OF CARIOUS LESION AND TEETH REMINERALIZATION according to claim 1 characterized by the cationic character of chitosan and the anionic character of fluoride enabling the property to form associations of fluorides chitosan type and soluble complexes of non-stoichiometric fluoride chitosan and the formation of complex and hybrid particles when chitosan is adsorbed on silver nanoparticles

5. PRODUCT FOR PREVENTION, INTERRUPTION OF CARIOUS LESION AND TEETH REMINERALIZATION according to claim 1 characterized by some polysaccharides being able to be dissolved with any heating up to 50 C. or directly in water, without the necessity of adding any organic acid.

6. PRODUCT FOR PREVENTION, INTERRUPTION OF CARIOUS LESION AND TEETH REMINERALIZATION according to claim 1 characterized by the presentation of the final product being able to be chosen among: A viscous liquid whose color depends on the optical properties of the particles of nanometric dimensions and their interactions with the environment in which it is dispersed. Solid films, which are directly obtained from liquid formulations through controlled evaporation of the solvent, followed or not by reticulation with alkaline vapors; A material in form of paste, obtained from wet films; A material in form of mass, which is obtained from wet films, which are folded and pressed until they acquire an aspect similar to a moldable mass.

7. PRODUCT FOR PREVENTION, INTERRUPTION OF CARIOUS LESION AND TEETH REMINERALIZATION according to claim 1 characterized by regardless the final product presentation, the application being able to be: topical on the surface of healthy teeth for prevention, as well as in cavities and tissues affected by carious lesion for treating and remineralization.

8. PROCESS FOR OBTAINING THE PRODUCT characterized by comprehending the following steps: Preparing a first aqueous solution containing metal ions concentrated in values ranging from 0.010 to 0.33 moles per liter; Preparing a second aqueous solution containing a reducing agent concentrated in values ranging from 0.015 to 1.250 moles per liter, which is chosen among hydrazine, sodium citrate, sodium borohydride, glucose, ascorbic acid, albumin, LiAlH4, boranes and some polysaccharides which may also perform this function; Preparing a third solution chosen among: dissolving a polysaccharide whose molar mass must be in a range of values between 20 and 10000 kDa in water; and dissolving a polysaccharide in an aqueous solution of an organic acid from 0.5 to 5.5%, adding 0.05 grams to 5.0 volumes of up to 500 mL, depending on the solubility of the polysaccharide; Submit solutions to temperature effects on a range of values between 3 C. to 60 C.; Mix the solutions to generate metal nanoparticles and whose resulting form is chosen among: adding the first solution to the third solution and then adding the second solution to the mixture; adding the second solution to the first solution and then adding the third solution; Adding a fluoride salt to the mixture of solutions in a form chosen among: dissolving the solid salt directly in the mixture and adding an aqueous solution of fluoride salt to the mixture; Adding a flavoring agent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0037] This invention is about a product designed to prevent the occurrence of lesions in teeth caused by dental caries, interrupt the development of such lesions, as well as promote the remineralization of the affected tooth and a process of obtaining this product.

[0038] The product gives the affected area a visually identifiable color, which enables, in some cases, monitoring evolution of the treatment over time.

[0039] The final product may be presented in liquid, mass or film form and, by the properties conferred by its components, it promotes an antimicrobial action, particularly bacteriostatic and bactericidal, with the capacity to prevent and stop the carious lesion together with the capacity to assist in teeth remineralization.

[0040] Once applied, the product gives the affected area a visually identifiable color, which enables, in some cases, monitoring the evolution of the treatment over time. The product enables or increases access to dental treatment, as it does not require an outpatient setting for its application. As this form of treatment does not involve invasive techniques for its application, the product is particularly recommended for treating children or people who react negatively to traditional places of dental intervention.

[0041] In the case of the applications proposed herein, it is exploited, in addition to its bacteriostatic and bactericidal properties, the visual aspect of formulations containing metal nanoparticles which enable the monitoring of the prophylaxis result, identifying more accurately the affected areas, with favorable aesthetic appearance.

[0042] In some cases, with time after the application of a varnish, the product presents visually identifiable color changes. This happens because the colloidal dispersions that contain metal particles of nanometric dimensions have various colors depending on the size distribution, shape, interaction with passivating/stabilizers molecules and the environment in which they are dispersed. This is a typical characteristic of the nanometric regime that results from oscillation of the so-called surface plasmons.

[0043] The composition of the product, one of the objectives of this invention, comprises the following components described below: [0044] 0.001% to 0.50% in metal particles selected among silver, gold, copper, gold/silver alloys and gold/copper alloys, present several morphologies such as spherical, elliptical, prisms, rods and plates, with dimension values ranging from 1 nm to 500 nm, are obtained from precursor compounds of metals through controlled reduction reactions, where the precursor compounds are selected among oxides, acetates, nitrates, acetyl acetonates, carbonate, chloride, citrate, fluoride, iodate, lactate, iodide, nitrite, perchlorate, phosphate, sulfate and trifluoroacetate; [0045] 0.03% to 6.0% of a polysaccharide chitosan with molar mass ranging between 20 kDa and 10,000 kDa, its derivatives, which are selected among: carboxymethyl chitosan, chitosan lactate, acetate chitosan, amylopectin, amylose, alginates, alginic acid, pectin, xylan, and chitin, other biopolymers selected from: methyl cellulose, carboxymethyl cellulose, cellulose acetate, hydroxyethyl cellulose and hydroxypropyl cellulose, and, additionally, salts deriving from alginic acid sodium, potassium or calcium; [0046] 0.05% to 2.0% of a fluoride salt, which tends to be associated with cationic sites of the polysaccharide obtained from water-soluble salts, from aqueous solutions with an acidic pH up to a maximum value of 6.0 in both stock solutions; [0047] 0.05% to 4.0% of an organic acid selected among lactic acid, acetic acid, citric acid, oxalic acid, ascorbic acid and other organic acids of general RCOOH structure, where R refers to an organic radical; [0048] 0.01% to 2.0% of a liquid dispersing agent based on water, with a slightly acid pH eventually increased with co-solvent, which is chosen among glycols such as propylene glycol, poly (ethylene glycol), including different molar masses, substituted glycols, co-solvents such as ethanol, isopropanol and polysorbates and other polymeric additives for controlling the viscosity derived from cellulose as hydroxy-propyl, methyl cellulose, hydroxy-propyl cellulose, carboxy methyl cellulose and methyl cellulose; [0049] 0.01% to 10% of a flavoring chosen among: peppermint, mint, cinnamon, eucalyptus, cherry, strawberry and red berries.

[0050] The metal particle is preferably the silver, and the stoichiometric ratio of metal ion to reducing agent ranges from 0.10 to 10.0.

[0051] The different forms of the product with its individual component options include the addition of medium or long chain polysaccharides that perform the following functions: [0052] antibacterial activity; [0053] increased physical and chemical stability for the compositions, which results in an increased expiration time for products; [0054] Stabilization of the nanoparticles resulting from interactions between the surface of the particles and functional groups and/or loads located in the structure of polysaccharides; [0055] ionic association with ions present in the composition and the ability to obtain compositions with higher concentration of active principle.

[0056] The cationic character of chitosan and the anionic character of fluoride enables the property to form associations of fluorides chitosan type and soluble complexes of non-stoichiometric fluoride chitosan and when chitosan is adsorbed on silver nanoparticles, complex and hybrid particles are formed.

[0057] Some polysaccharides can be dissolved with any heating up to 50 C. or directly in water, without the necessity of adding any organic acid.

[0058] The presentation of the final product may be chosen among: [0059] A viscous liquid whose color depends on the optical properties of the particles of nanometric dimensions and their interactions with the environment in which it is dispersed. It is already known by experts that the optical properties of the particles of nanometric dimensions depend on its size, geometry and size distribution and geometric shape for each component option of the composition. For example, a composition containing gold may be yellow or brownish, while another composition containing gold may also be red, blue or purple, depending on the other components involved; [0060] Solid films, which are directly obtained from liquid formulations through controlled evaporation of the solvent, followed or not by reticulation with alkaline vapors; [0061] A material in form of paste, obtained from wet films; [0062] A material in form of mass, which is obtained from wet films, which are folded and pressed until they acquire an aspect similar to a moldable mass.

[0063] Regardless the final product presentation, the application can be: topical on the surface of healthy teeth for prevention, as well as in cavities and tissues affected by carious lesion for treating and remineralization.

[0064] The process for obtaining the product and to prevent the interruption of carious lesion and teeth remineralization, the second object of the present invention, will be described below and can be observed that it comprises the following steps: [0065] Preparing a first aqueous solution containing metal ions concentrated in values ranging from 0.010 to 0.33 moles per liter; [0066] Preparing a second aqueous solution containing a reducing agent concentrated in values ranging from 0.015 to 1.250 moles per liter, which is chosen among hydrazine, sodium citrate, sodium borohydride, glucose, ascorbic acid, albumin, LiAlH4, boranes and some polysaccharides which may also perform this function; [0067] Preparing a third solution chosen among: [0068] dissolving a polysaccharide whose molar mass must be in a range of values between 20 and 10000 kDa in water; and [0069] dissolving a polysaccharide in an aqueous solution of an organic acid from 0.5 to 5.5%, adding 0.05 grams to 5.0 volumes of up to 500 mL, depending on the solubility of the polysaccharide; [0070] Submit solutions to temperature effects on a range of values between 3 C. to 60 C.; [0071] Mix the solutions to generate metal nanoparticles and whose resulting form is chosen among: [0072] adding the first solution to the third solution and then adding the second solution to the mixture; [0073] adding the second solution to the first solution and then adding the third solution; [0074] Adding a fluoride salt to the mixture of solutions in a form chosen among: dissolving the solid salt directly in the mixture and adding an aqueous solution of fluoride salt to the mixture; [0075] Adding a flavoring agent.

[0076] The final product obtained through the process above, through its characteristics, has the following advantages: [0077] greater efficiency for the prevention and eradication of dental caries in comparison to currently used products and with a similar application method; [0078] the silver content may be up to 17 times lower than the silver diammine fluoride commercially used in products; [0079] metal nanoparticles provide an acceptable visual appearance, inexistent in comparable technologies. The total content of silver is up to 600 times smaller than in the SDF to obtain the same clinical effect; [0080] overall, the evolution of the treatment can be monitored over time, from visual inspection and color identification of the compromised areas indicating, also, the necessity for new applications; [0081] the high viscosity of the end product prevents the product flowing to unwanted areas, and avoids the subsequent formation of spots on the skin of the patient or professional; [0082] low cost compared to treatments carried out in offices; [0083] the product does not require a dental clinic equipped for application and does not require the use of drills or procedures requiring anesthesia, because its application is painless; [0084] simple application, which can be performed with brush or through direct application of membrane or mass.

[0085] Some examples involving preparation aspects in some of the stages of the process for obtaining the final product and results observations will be presented below.

EXAMPLE 1

[0086] Addresses the chemical reduction of silver ions with sodium citrate, using AgNO3 as a precursor, where 90 mg of AgNO3 were dissolved in 500 mL of deionized water and the solution was heated to boiling under magnetic stirring. Then, 10 mL of sodium citrate solution at 1% (w/v) were added. The solution was kept under stirring and boiled for 1 hour. The nanoparticles synthesized by this method presented an absorption maximum at approximately 420 nm in the UV-visible absorption spectrum.

EXAMPLE 2

[0087] 100 ml of an aqueous ascorbic acid solution (6104 molL1) were used, sodium citrate (3103 M) and the pH was controlled in the range 6.0 to 10.5 by adding 0.2 M of HNO3 or 0.1 M of NaOH. The system was heated to 35 C. under magnetic stirring and 1 ml of a 0.10 M solution of AgNO3 was added. The solution turned brown for the synthesis with pH =10.5 and blurred blue for those with pH <10.5.

EXAMPLE 3

[0088] For the synthesis of seeds, in a solution 4104 M of AgNO3, under magnetic stirring and room temperature, 1 mL of 0.072 M of NaBH4 was quickly added, immediately turning the solution yellow after its addition. Thus, many nuclei (seeds) were generated, which were stabilized by chitosan and served for the growth of larger nanoparticles. For the growth of the silver nanoparticles (AGNPS), initially in 50 mL of a 4.0104 M of AgNO3 solution and 20.0104 M of sodium citrate, under magnetic stirring and room temperature, different amounts of seed (10.0L3.0mL) and 1.0 mL of a 2.0103 M solution of ascorbic acid were added. In this case, the addition of ascorbic acid had to be carried out slowly and the final size and shape of the AgNPs at the end of the synthesis depended on the amount of seeds, or in other words, small quantities of seeds result in higher AgNPs and large quantities of seeds results in lower AgNPs.

EXAMPLE 4

[0089] To prepare the colloid, 1.0 gram of chitosan was dissolved in 200 ml of acetic acid solution at 2% (v/v). The solution was kept overnight under stirring and then the solution was vacuum filtered. It was later taken one aliquot of 60 mL of chitosan solution and placed in an ice bath under stirring. Then, 4.0 mL of a 0.012 molL1 silver nitrate solution were added and 30 more minutes were included before adding sodium borohydride. The relationship between AgNO3 and NaBH4 was maintained 1:6 in mass with dropwise addition. The reduction of Ag+ was started immediately, the color of the solution changed from colorless to light yellow and finally red. After synthesis, the colloid remained in the ice bath for 45 minutes. After this period, the colloid was taken out of the ice bath colloid and we waited for it to reach the room temperature before the optical absorption measurements. Immediately after the synthesis, the samples were stored in vials protected with aluminum foil and were and kept in the refrigerator.

[0090] Although the present invention has been described in its preferred embodiment, the main ideas guiding the present invention which are a product designed to prevent the occurrence of lesions in teeth caused by dental caries, interrupt the development of such lesions, as well as promote remineralization of the affected tooth and a process for obtaining this product remains preserved as to its innovative character, where those usually skilled in the technique may discern and practice variations, modifications, alterations, adaptations and equivalents that are suitable and compatible to the working environment in question without, however, departing from the comprehensiveness of the spirit and scope of the invention, that are represented by the following claims.