RU2691960C1 - Hydrogel for remineralisation of hard dental tissues - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, namely to dentistry, and can be used for remineralisation of hard dental tissues in order to prevent and treat caries in the stain stage, hyperesthesia of hard dental tissues. Disclosed hydrogel contains, wt %: hydroxyapatite 10.0–15.0; xylitol 10.0–15.0; papain 3.0–5.0; potassium nitrate 3.0–5.0; carbopol 0.5–1.0; sodium hydroxide 10 % solution 2.0–3.0; sorbic acid 0.2–0.5; fragrance 0.3–0.5; highly pure water – balance.EFFECT: use of the agent provides higher acid resistance of the enamel, eliminates and prevents the progressing of the dental tissue demineralisation processes, reduced sensitivity, prolonged remineralisation effect due to prolonged contact of the remineralising gel with the surface of dental hard tissues, increased efficiency of therapeutic and preventive measures and reduced length of their carrying out.1 cl, 4 tbl, 4 ex, 2 dwg

Description

The present invention relates to medicine, namely to dentistry, and can be used for the remineralization of hard dental tissues for the prevention and treatment of caries in the stage of stains, hyperesthesia of hard dental tissues.

Despite the development of preventive dentistry, caries still remains one of the most common pathologies and affects up to 100% of the adult and child population. Enamel caries (“white spot” stage or focal demineralization) is the form of the disease in which it is possible to stop the progression of demineralization and destruction of hard dental tissues. The lack of timely treatment is accompanied by the development of infectious complications, which often causes the removal of teeth and leads to dysfunction and aesthetics of the dentofacial system.

Another equally common pathology is tooth sensitivity (hyperesthesia), which occurs with lesions not associated with or associated with loss of enamel and dentin. Hyperesthesia occurs after the procedures of professional oral hygiene and whitening, accompanied by non-carious lesions of hard tissues that occur after eruption (increased abrasion, wedge-shaped defect, erosion). The non-invasive and effective methods of prevention and treatment of focal demineralization of enamel, hyperesthesia of teeth of various etiologies include remineralizing therapy.

Known composition for the prevention of diseases of the oral cavity, which contains the following components, wt. %: glycerin 20-25, xylitol 10-14, silicon dioxide 22-26, xanthan gum 1.2-1.4, methyl paraben 0.2-0.3, propyl paraben 0.08-0.12, sodium saccharin 0, 1-0.3, titanium dioxide 0.2-0.4, perfume 0.7-1.0, bromelain 0.1-0.7, sodium lauryl sulfate 1.2-1.4 or alkylamidobetaine 3.5, calcium glycerophosphate 0.6-1.0, magnesium chloride 0.08-0.16 or magnesium glycerophosphate 0.16, drinking water up to 100 (RF Patent No. 2293551, published February 20, 2007).

Advantages: the presence in the composition of glycerophosphate calcium or magnesium as a source of calcium, magnesium and phosphorus, xylitol as an anticariogenic component, bromelain to improve the cleansing of tissues.

The disadvantages are the low concentration of calcium and magnesium glycerophosphate, which reduces the therapeutic efficacy of the composition, the absence of desensitizing components (does not help to eliminate hyperesthesia), the presence of abrasive compounds (titanium and silicon dioxide), the content of sodium lauryl sulfate, which has irritating properties (may cause dry mouth, aft and erosion).

Known composition comprising the following components, wt. %: glycerin 8-15, sorbitol 8-15, xylitol 8-18, hydroxyethylcellulose 1.5-2.8, polysorbate 0.6-1.2, methyl paraben 0.2-0.3, calcium glycerophosphate 0.7- 1.9, magnesium chloride 0.06-0.20, guar gum 0.06-0.15, perfume 0.3-0.6, drinking water up to 100 (RF Patent No. 2311168, published on November 27, 2007).

The disadvantage is the low concentration of calcium compounds, the absence of enzymes and desensitizing components, which reduces the effectiveness of remineralization of hard tissues, and also does not contribute to the elimination of hyperesthesia. The positive quality of this composition is the presence in the composition of glycerophosphate as a source of calcium and phosphorus, xylitol as an anticariogenic component, the consistency and form of release in the form of a gel, the possibility of use in kappa.

The closest in essence, adopted for the closest analogue composition, comprising the following components, wt. %: hydroxyapatite - 2.0-20.0, chlorhexidine bigluconate (antiseptic preparation) - 0.05-0.5, tizol (aqua complex of titanium glycerosolvate) - the rest (RF patent №2216304 published on November 20, 2003).

The advantage of the closest analogue: the presence in the composition of hydroxyapatite as a source of calcium and phosphorus, as insulated as a transport basis.

The disadvantages of the closest analogue are: short-term contact with the tooth tissues is carried out only during rubbing for 3 minutes; the need for rinsing after the use of the composition of the oral cavity; chlorhexidine content can cause tooth staining and impairment of oral microflora with prolonged use; preparation of the composition immediately before use.

The objectives of the invention is to increase the acid resistance of enamel, the elimination of demineralization processes and the reduction of the increased sensitivity of hard dental tissues.

The essence of the proposal is a hydrogel for remineralization of hard dental tissues containing hydroxyapatite, characterized in that it additionally contains xylitol, papain, potassium nitrate, carbopol, sorbic acid preservative, stabilizer sodium hydroxide solution and perfume in the following ratio, mass% :

Hydroxyapatite 10.0-15.0 Xylitol 10.0-15.0 Papain 3.0-5.0 Potassium nitrate 3.0-5.0 Carbopol 0.5-1.0 Sodium hydroxide solution 10% 2.0-3.0 Sorbic acid 0.2-0.5 Odorant 0.3-0.5

Highly purified water else

EFFECT: increased acid resistance, resistance of hard tissues of teeth, reduction of enamel solubility, prevention of focal demineralization, treatment of enamel caries in the “white spot” stage, reduction of hyperesthesia, prevention of progression of carious process, prolongation of the remineralization effect due to prolonged contact of the remineralizing hydrogel with the surface of solid tissues teeth, improving the effectiveness of treatment and preventive measures and reducing their duration.

The choice of components of the composition is based on their physicochemical and biological properties.

Hydroxyapatite (HAP) is represented by ultrafine white powder of high purity. The chemical formula is Ca ₁₀ (PO4) ₆ (OH) ₂ . It is the main structural component of enamel and dentin. It is characterized by biological compatibility with human tissues. Hydroxyapatite is embedded in the structure of hard tissues, forms a protective layer on the surface of enamel and dentin, fills microdefects, cracks, obtures dentinal tubules. This effect provides an increase in acid resistance, resistance of hard dental tissues, a decrease in enamel solubility, contributes to the prevention and treatment of focal demineralization, reduction of hyperesthesia, prevention of progression of the carious process.

Xylitol (xylitol) is a polyhydric alcohol, a sweetener, improves the organoleptic properties of the gel, performs the function of a water-holding agent, has anti-cariogenic properties. The mechanism of action of xylitol is due to the following factors:

1. The absence of enzymes that break down xylitol in microorganisms leads to its excessive accumulation inside the cell and, as a result, causes its lysis - “lethal synthesis”.

2. Xylitol contributes to an increase in the activity of salivary lactoperoxidases, enzymes that promote the lysis of cariogenic microorganisms.

3. Xylitol reduces the adhesion of cariogenic microorganisms to hard dental tissues, prevents the formation of dental plaque.

4. Xylitol accelerates salivation, increases the buffer and remineralizing functions of saliva.

Potassium nitrate - has desensitizing properties due to the fact that potassium ions diffuse into the dentinal tubules, accumulate in them and depolarize the membrane of nerve fibers. Due to its high concentration, the membrane cannot repolarize and the conduction of the pain impulse is blocked.

Papain is a natural enzyme extracted from papaya fruits, has a high proteolytic activity, breaks down peptide bonds between amino acid residues in protein molecules. This property of the enzyme leads to the suppression of the vital activity of dental plaque microorganisms, besides forming a thin film on the surface of hard tissues of teeth, papain reduces the adhesive ability of microflora. One of its properties is to increase the activity of remineralization processes.

Carbopol is a high molecular weight polymer of acrylic acid. It is a white, hygroscopic powder of a weakly acidic reaction, swelling in water and other solvents. Forms stable gels when neutralized with alkaline solutions.

Carbopol plays the role of gelling, ensures the stability of the formulation. The gel based on it does not exfoliate, does not dry out, does not crumple, does not change color. Carbopol is easy to use: it dissolves well in water, it is easily mixed with any active ingredients. Advantages of carbopol: thermal and microbiological stability, storage stability, compatibility with various active substances, hypoallergenic, do not irritate the fabric, the possibility of obtaining gels of different viscosity.

Sodium hydroxide (stabilizer) - alkali, acts as a neutralizer in the formation of a gel based on carbopol.

Sorbic acid is a preservative that meets the safety requirements for the body. Sorbic acid exhibits high antimicrobial properties, has no toxicity, carcinogenicity, is not an allergen, does not change the organoleptic properties of related compounds, does not irritate the skin and mucous membranes. Its action is directed mainly against yeast and mold fungi. Sorbic acid inhibits the enzymes of carbohydrate metabolism of microorganisms, destroys their cell membranes. In addition to the properties of the preservative, it exhibits the properties of a moisturizing component and a plasticizer, therefore it is widely used in various dosage forms.

Selection of the mass fractions of the components used was carried out experimentally. It is established that the use of components outside the specified range does not improve the clinical effect.

The combination of hydroxyapatite, xylitol, papain and potassium nitrate provides anticariogenic properties, desensitizing effect, speeds up the process of remineralization, contributes to increasing resistance, reducing the acid solubility of hard dental tissues. Introduction to the formulation of hydroxyapatite, due to the release of calcium and phosphorus, ensures the filling of microdefects, free interprismatic spaces, enamel cracks, obstruction of the dentinal tubules, promotes the remineralization of demineralized enamel foci. The papain contained in the composition breaks the peptide bonds of glycoproteins and proteoglycans and contributes to the effectiveness of the remineralizing properties of the composition. Potassium nitrate depolarizes the nerve fiber membrane and blocks the conduction of pain impulse. Xylitol stimulates salivation, increases the buffer and remineralizing functions of saliva, reduces the adhesion of cariogenic microorganisms, prevents the formation of dental plaque, causes lysis of bacterial cells. The use of carbopol as a base contributes to the formation of a uniform, chemically stable, safe and convenient form of the prepared composition. And the use of sorbic acid as a preservative makes the composition safe for use by patients of different contingents. The absence of alcohol and other strong antiseptics eliminates the possibility of dehydration of tissues, which is often the cause of hypersensitivity when using various fluorine-containing drugs.

The proposed tool is made in the form of a translucent white gel, which eliminates unwanted staining of hard tissues, is easily applied to the surface of hard tissues of teeth and fills cracks, microdefects, open dentinal tubules.

New features that meet the criteria of "novelty" in the proposed invention are, in our opinion, the composition of the composition and the mass ratio of components.

Indications for use of the proposed means:

1. Prevention of caries in the stage of “white spot” (focal demineralization)

2. Treatment of caries in the “white spot” stage

3. Hyperesthesia of teeth of various etiologies.

The composition is obtained in the following way: take 55-71 ml of highly purified water, on the surface of which gently pour 0.5-1 g of carbopol, mix and leave to swell for 6-8 hours. Then the temperature of the mixture is raised to 60 degrees and stirred for 20-30 minutes until the polymer is completely dissolved. To the finished solution of carbopol is added a thin stream of 2.0-3.0 g of 10% sodium hydroxide solution. Mixing is carried out until a gel-like mass is homogeneous over the entire volume within 30-40 minutes. In the remaining volume of purified water, 10-15 g of xylitol, 3-5 g of potassium nitrate, 0.2-0.5 g of sorbic acid, 3- 5 g of papain, 0.3-0.5 g of odorant. The resulting solution is filtered and added to a solution of carbopol, stirred for 20-30 minutes until smooth. In a separate container, 10-15 g of hydroxyapatite are placed, slightly triturated, and 5-7.5 g of a previously prepared mixture of carbopol and gel components are added. Mix to obtain a homogeneous suspension concentrate, to which 77.5-85 g of the solution of carbopol and gel components are gradually added. The prepared composition is finally homogenized, thoroughly mixed. Get a hydrogel.

Method of applying remineralizing hydrogel:

1. The remineralizing composition is applied to the surface of hard dental tissues with a micro applicator, then rubbed into the dental tissue at low revs (2000 rpm) with a circular brush for 2-3 minutes.

2. The hydrogel is used with a standard or individual kappa for prolonging remineralization, exposure time 15 minutes.

Eating and drinking is recommended no earlier than 1 hour after the procedure. The course of prophylaxis or treatment includes from 3 to 12 procedures, depending on the clinical situation, if necessary, it is repeated after 6-12 months.

Clinical testing was carried out on the basis of the dental clinic FGBOU VO KUBGMU MZ RUSSIA. In total, 32 patients were diagnosed and treated with a diagnosis of “caries in the spotting stage” and 29 patients diagnosed with “hyperesthesia of hard dental tissues”.

The results of clinical observation of the action of the proposed hydrogel for remineralization of hard dental tissues were compared with data obtained using fluorine-containing preparations, which are often used in modern practice.

The main group (the proposed hydrogel for remineralization).

The comparison group (ftorgel “Sultan Torekh“ 00:60 ”Second”).

The results of the comparison are presented in table 1, 2, 3, 4.

p * - statistically significant accuracy adopted at p <0.05

p * - statistically significant accuracy adopted at p <0.05

The results of clinical studies indicate the effectiveness of the proposed hydrogel for remineralization.

Examples of the preparation of a hydrogel for remineralization.

Example number 1. To prepare the portion of the proposed hydrogel, 71.0 ml of highly purified water was taken, on the surface of which gently poured 0.5 g of carbopol, stirred and left to swell for 6-8 hours. Then the temperature of the mixture was raised to 60 degrees and stirred for 20-30 minutes until complete dissolution of the polymer. To the finished carbopol solution, a thin stream of 2.0 g of 10% sodium hydroxide solution was added. Mixing led until a homogeneous throughout the volume of the gel-like mass within 30-40 minutes. In the remaining volume of purified water, 10.0 g of xylitol, 3.0 g of potassium nitrate, 0.2 g of sorbic acid, 3.0 g of papain, 0.3 g of odorant were successively dissolved. The resulting solution was filtered and added to the carbopol solution, stirred for 20-30 minutes until smooth. 10 g of hydroxyapatite were placed in a separate container, slightly triturated, and 5-7.5 g of a previously prepared mixture of carbopol and gel components were added. Mixed until a homogeneous suspension concentrate is obtained, to which 77.5-85 g of the solution of carbopol and gel components are gradually added. The prepared composition was finally homogenized, thoroughly mixed.

Example number 2. To prepare a portion of the proposed hydrogel, 55.0 ml of highly purified water was taken, on the surface of which gently poured 1.0 g of carbopol, stirred and left to swell for 6-8 hours. Then the temperature of the mixture was raised to 60 degrees and stirred for 20-30 minutes until complete dissolution of the polymer. 3.0 g of 10% sodium hydroxide solution was added to the finished carbopol solution in a thin stream. Mixing led until a homogeneous throughout the volume of the gel-like mass within 30-40 minutes. In the remaining volume of purified water, 15 g of xylitol, 5 g of potassium nitrate, 0.5 g of sorbic acid, 5 g of papain, 0.5 g of odorant were successively dissolved. The resulting solution was filtered and added to the carbopol solution, stirred for 20-30 minutes until smooth. 15 g of hydroxyapatite were placed in a separate container, slightly triturated, and 5-7.5 g of a previously prepared mixture of carbopol and gel components were added. Mixed until a homogeneous suspension concentrate is obtained, to which 77.5-85 g of the solution of carbopol and gel components are gradually added. The prepared composition was finally homogenized, thoroughly mixed.

Examples of the use of the composition as intended.

Example 3. Patient C., 25 years old, Amb. Card No. 19920p complained of sharp pains in the area of the anterior teeth of the upper jaw that occur when exposed to chemical and thermal irritants. Objectively: the frontal teeth of the upper jaw are intact. The thermal test is painful, the reaction is short-term, the indicators of electrical donor diagnostics are within the normal range of 3-5 µA. The average intensity of the carious process KPU = 11 Hygienic index ОHI-S = 1,3 (satisfactory oral hygiene). The index of the prevalence of hyperesthesia of teeth (IRGS) = 53%, the index of the intensity of hyperesthesia of teeth (IIHP) = 2.2 points.

Diagnosis: generalized form of hyperesthesia, II degree.

Treatment: under application anesthesia (spray Lidoxor) and 4% - 1.7 ml articaine infiltration solution, professional oral hygiene was performed, the teeth were isolated from saliva. The proposed composition was applied and rubbed with a circular brush at low speed 2000 rpm for 2-3 minutes. Further, the composition was added to the standard tray for the prolongation of the application for 15-20 minutes. A complete treatment course (10 applications) was carried out using the proposed hydrogel for remineralization.

When re-examining after the end of the course of treatment, there are no complaints of pain when exposed to temperature and chemical irritants, the index of the prevalence of hyperesthesia of the teeth (IRGP) = 0, the intensity index of the hyperesthesia of the teeth (IIHP) = 0 points. The obtained data confirm the therapeutic effect of the applied composition, namely, increasing acid resistance, resistance of hard dental tissues, reducing enamel solubility, eliminating hyperesthesia, prolonging the remineralization effect due to prolonged contact of the remineralizing hydrogel with the surface of hard dental tissues, improving the effectiveness of therapeutic and preventive measures.

Example 4. Patient C, 24 years old, Amb. Map № 21223п complained of white spots of the front teeth of the upper jaw on the left. According to the patient, 22 and 23 teeth were not previously treated.

Objectively: on the vestibular surface of the 22nd and 23rd teeth there are foci of demineralization of whitish color. Their surface during sounding is rough. Indicators of vital staining on a 10-point scale of blue = 8 points (Fig. 1, p. 1). Indicators of the laser-fluorescent method (the device DiagnoDent "KaVo", Germany) = 19 units, which corresponds to the initial carious process.

Diagnosis: enamel caries acute for 22 and 23 teeth.

Treatment: held professional oral hygiene, teeth isolated from saliva. The proposed hydrogel was applied and rubbed using a circular brush at low speeds of 2000 rpm for 2-3 minutes. Further, the composition was added to the standard tray for the prolongation of the application for 15-20 minutes. A complete treatment course (10 applications) was carried out using the proposed hydrogel for remineralization. The patient is given advice on oral hygiene.

When re-examination after 1 month, the indicator of vital staining = 2 points (Fig. 2, p. 2). Indicators of the laser-fluorescent method (the device DiagnoDent "KaVo", Germany) decreased to 8 units. The obtained data confirm the therapeutic effect of the applied composition, namely, increasing acid resistance, resistance of hard dental tissues, reducing enamel solubility, preventing progression of focal demineralization and treatment of enamel caries in the “white spot” stage, prolonging the remineralization effect due to prolonged contact of the remineralizing hydrogel with the solid surface dental tissues, improving the effectiveness of therapeutic and preventive measures.

The obtained data of the study indicate the clinical effectiveness of the proposed hydrogel, which allows it to be recommended for remineralization of hard dental tissues for the prevention and treatment of caries in the staining stage, hyperesthesia of hard dental tissues. The proposed hydrogel for remineralization of hard tissues of teeth has pleasant organoleptic properties for the patient and does not cause discomfort, has no side effects and contraindications to use, and, thus, can find active use in preventive and therapeutic dentistry, increasing the range of remineralization means beneficial to the economic points of view.

Claims (3)

Hydrogel for remineralization of hard tissues of teeth containing hydroxyapatite, characterized in that it additionally contains xylitol, papain, potassium nitrate, carbopol, sorbic acid preservative, stabilizer sodium hydroxide solution and perfume in the following ratio, wt. %: Hydroxyapatite                       10.0-15.0 Xylitol                                   10.0-15.0 Papain                                       3.0-5.0 Potassium nitrate                                       3.0-5.0 Carbopol                                       0.5-1.0 Sodium hydroxide solution 10%   2.0-3.0 Sorbic acid                            0.2-0.5 Odorant                                        0.3-0.5 Highly purified water else

Images