WO2021025585A1

WO2021025585A1 - Use of dendrimers in agents for care of the teeth and oral cavity

Info

Publication number: WO2021025585A1
Application number: PCT/RU2019/000913
Authority: WO
Inventors: Елена Юрьевна БЕЛОУС; Ирина Евгеньевна ЯГАФАРОВА
Original assignee: Общество С Ограниченной Ответственностью "Сплат Глобал"
Priority date: 2019-08-08
Filing date: 2019-12-20
Publication date: 2021-02-11

Abstract

The invention relates to a novel use of a dendrimer for enhancing the remineralizing effect of calcium-containing agents for care of the teeth and oral cavity.

Description

APPLICATION OF DENDRIMERS IN TOOTH CARE AND

ORAL CAVITY

FIELD OF TECHNOLOGY

The present invention relates to a new use of dendrimers for enhancing the remineralizing effect of calcium-containing dental and oral care products.

The state of the oral cavity depends on the state of a number of mechanisms for the regulation of biological processes. The composition of salivary fluid, local immune status and associated changes in the microbiota are key factors in ensuring the normal functioning of the upper digestive tract. At the same time, these factors are influenced by external influences - a diet with a predominance of simple carbohydrates, smoking, a number of nosologies lead to disruption of the homeostasis of systems that ensure oral health (Kinane DF, Stathopoulou P G, Papapanou P N. Periodontal diseases. Nat Rev Dis Primers 2017; 3: 17038; Acharya A, Chan Y, Kheur S et al. Salivary microbiome in non-oral disease: A summary of evidence and commentary. Arch Oral Biol. 2017; 83: 169-173). As a result, such an imbalance provokes various diseases in the oral cavity, of which the most acute are caries and periodontitis associated with changes in the species composition of the microbiota and bacterial metabolism (Tanner A.S., Kressirer S.A., Faller LL Understanding Caries From the Oral Microbiome Perspective. Journal of the California Dental Association, 2016; 44 (7): 437-446, 10; Marsh PD, Head DA, Devine DA. Ecological approaches to oral bio films: control without killing. Caries Res 2015; 49 (suppl l ): 46-54; Arweiler NB, Netuschil L. The Oral Microbiota. Microbiota Hum. Body, Springer International Publishing; 2016, p. 45-60). Their course can be complicated in case of violation of the mineral and metabolic composition of saliva. So, in particular, a change in the concentrations of acetic, formic, propionic, pyruvic, lactic acids, glycine, methanol, acid, propylene glycol, taurine, ATP, adenine in salivary fluid was noted under a number of conditions (Takeda I, Stretch C, Bamaby P et al Understanding the human salivary metabolome NMR Biomed 2009; 22 (6): 577-84).

An example of another disease associated with a dysfunction of local mucosal immunity is recurrent aphthous stomatitis - the most common ulcerative lesion of the mucous membrane, covering up to 50% of the population. The appearance of ulcerative defects is accompanied by an increase in lymph nodes, burning sensation and, in some cases, fever. The duration of the disease is usually 4 to 14 days and significantly affects the quality of life; the frequency of relapses can be up to four times a month (Akintoye SO, Greenberg MS. Recurrent aphthous stomatitis. Dent Clin North Am. 2014; 58 (2): 281-97).

The epidemiology of dental diseases is extremely broad and covers multiple groups of the population, regardless of social status. Patients, to the greatest extent, are concerned about the reaction of the teeth and mucous membranes to temperature, food irritants, as well as concern about the manifestations of halitosis.

The issues of etiology, pathogenesis and treatment of dentin hyperesthesia are an urgent problem of modern dentistry. Tooth sensitivity is one of the most popular reasons for visiting a dentist. Hyperesthesia is one of the most common dental diseases and, according to WHO, has become widespread in the world. According to researchers, 40-70% of the population aged 20 to 65 years suffers from various forms of hyperesthesia of hard dental tissues (Takeda I, Stretch C, Bamaby P et al. Understanding the human salivary metabolome. NMR Biomed. 2009; 22 (6): 577-84).

The main reason why hyperesthesia (hypersensitivity) occurs is enamel thinning, demineralization. Enamel belongs to mesoporous substances, it does not contain cells and is not capable of regeneration in case of damage, however, there is a constant exchange of mineral ions that come from saliva through the pores and are adsorbed on its surface, which makes it possible to carry out remineralizing therapy. The fundamental local factor in the development of this pathology is a local change in pH on the surface of the tooth due to the accumulation of plaque on it, containing acid-forming streptococci (Streptococcus mutans, S. sanguis, St. mitis, St. salivarius), which are characterized by anaerobic fermentation, and some lactobacilli ( Makarova N.E. Vinnichenko Yu.A. Focal demineralization of enamel. Methods of diagnosis and treatment. Dentistry. - 2017. - N 4. - P.67-71).

Demineralization of enamel is characterized by a change in its color, deformation and a lack of characteristic gloss due to deviations in the surface relief of the tooth enamel. Most often, the problem occurs due to improper dental care, smoking, the use of highly abrasive toothpastes, the use of sugary carbonated drinks and confectionery, as well as due to pregnancy. So, the enamel loses minerals and does not have time to recover, because of which the teeth become sensitive. It is difficult for people with such a problem to lead their usual lifestyle, since constant toothaches when drinking cold and hot drinks, juices, vegetables and fruits, when communicating in the fresh air cause severe discomfort. Enamel strengthening products containing calcium for enamel mineralization are capable of solving this problem, however, there are currently no products on the market that have a prolonged effect. Most of the products presented only mask the problem of sensitive enamel, for example, the use of potassium salts in agents for the prevention and normalization of oral conditions, allows you to reduce the activity of nerves for a while, but then the sensitivity of the enamel returns.

Most often, hypersensitivity is observed in diseases of non-carious origin (abrasion, pathological abrasion, erosion, less often with wedge-shaped defects), in which there is a significant loss of enamel and dentin is exposed. With carious defects, as well as with initial caries, especially when it is localized in the cervical region, pain may occur, which is associated with the demineralization of the enamel under the action of acids and an increase in its permeability. Hyperesthesia is observed in traumatic injuries of the hard tissues of the teeth: chipping, cracks, coronal-root fractures of the tooth. Increased sensitivity of enamel, as a complication, can occur after teeth whitening procedures. In particular, professional whitening leads to the outflow of macro- and microelements from the enamel, which leads to an increase in the permeability of the enamel, resulting in sensitivity. Moreover, the less stable the enamel (the higher the level of caries intensity), the higher the risk of this complication. With recession of the gums, exposure of the necks of the teeth, which occur in various conditions and, above all, in periodontal diseases, both inflammatory and dystrophic in nature, the symptom of sensitivity is observed quite often. The recession of the gums, in addition to periodontal diseases, is the result of mechanical injuries, the presence of a short frenum of the upper and lower lips, the development of a small vestibule of the oral cavity, occlusion disorders, poor-quality manufacturing of dentures and crowns, the use of a toothbrush with stiff bristles, as well as incorrect (horizontal) and aggressive movements when brushing teeth, traumatic and improper use of dental floss, lack of gum isolation during whitening. Hypersensitivity of the teeth can also occur after traumatic professional hygiene (damage to the enamel with tools, excessive polishing, especially in the area of the neck and root of the tooth). Besides pain reaction resulting from local causes and irritants, an unwanted excessive reaction of the immune system can also occur in connection with some pathological conditions of the body (the so-called systemic or functional hyperesthesia): psychoneuroses, endocrinopathies, diseases of the gastrointestinal tract, metabolic disorders, age-related hormonal changes and disorders, infectious and other concomitant diseases [The use of desensitizers with increased sensitivity of the teeth. Zhurbenko VA, 2016, Kursk State Medical University M3 RF, Department of Pediatric Dentistry].

To prevent hyperesthesia of tooth enamel, it is necessary to exclude harmful external factors: normalization of the diet, cessation of smoking, adherence to the principles of a healthy lifestyle in general, and the use of hygiene products that have a multi-complex effect - toothpastes, rinses, and others. Means of this kind should not only help to clean the surface of the teeth from plaque, but also contribute to the prevention of caries, the prevention of gingivitis and periodontitis (anti-inflammatory effect). Nevertheless, no means that effectively provide a complex effect, consisting in normalizing the metabolome and pH of salivary fluid, enhancing the remineralizing function of salivary fluid and optimizing the composition of the microbiota, preventing aphthous stomatitis and immunomodulation, has not been described to prolong the described effects.

Thus, it is obvious that there is an urgent need for such a tool aimed at reducing the sensitivity of the enamel due to its durable strengthening and restoration of the metabolic process of calcium ions in the oral cavity. While investigating the properties of various promising molecules and their potential for use in dental and oral care, the authors unexpectedly found an increase in the remineralizing effect of calcium-containing dental and oral care products when dendrimers are added to their composition.

Dendrimers are called molecules with a symmetrical tree-like structure.

The main difference between dendrimers and other objects of the nanoscale is in the methods of controlling their structure and properties. Due to the fact that the sizes of dendrimer macromolecules can be predicted and controlled with high accuracy, they can be ideal standards in mass spectrometry, electron and atomic spectroscopy, and ultrafiltration. The presence of channels and pores in macromolecules of dendrimers allows them to be used for encapsulation and immobilization of "guest" low-molecular-weight molecules, including physiologically active. The area of application of dendrimers has expanded significantly due to the discovery of their liquid crystal ordering. It was shown that the mesogenic groups responsible for it can be located both inside and on the periphery of dendrons. Liquid crystal dendrimers are used in nanotechnology as new materials, in medicine as carriers of drugs and in other fields of science and technology, where molecules are needed - particles several nanometers in size, capable of ordering and changing their properties under the influence of external fields. Of great interest for biochemistry are dendrimers, in which a metal atom with vacant orbitals acts as a nucleus. Thus, the dendrimeric technology was used in the synthesis of iron (II) dendrimeric porphyrins as models of hemoglobin, which have a higher (1500 times) constant of reversible oxygen binding compared to human hemoglobin, in which iron porphyrin (heme) is surrounded by a globular protein (globin). In both cases, oxygen fixation occurs as a result of its coordination on the iron atom. It is assumed that a concomitant factor responsible for the greater affinity of oxygen for dendrimeric porphyrins is the formation of hydrogen bonds by oxygen molecules with amide groups of the first generation of the dendrimer. A high degree of functionality creates unlimited opportunities for further transformations of dendrimer macromolecules, which can lead to the design of new nanoscale structures, modification of the surface of macromolecules in order to give them pronounced lyophobic or lyophilic properties, and the creation of a new type of supported catalysts. Thus, the main achievements of dendrimer chemistry open up great opportunities for their use in various fields (Zakharova OG et al. Dendrimers: synthesis, properties, application. Teaching materials for the advanced training program "New materials of electronics and optoelectronics for information and telecommunication systems "Nizhny Novgorod State University named after NI Lobachevsky. Nizhny Novgorod, 2006. 87 p.).

The dendrimers and dendrite-like polymers synthesized to date are viscous liquids or amorphous solids, readily soluble in most known organic solvents. Unlike chain polymers, they are not characterized by a crystalline state; however, liquid crystalline ordering is possible in solutions and melts of polymers containing mesogenic groups. The physical and mechanical properties of dendrimers and dendrite-like polymers have not been systematically studied. Dendrimers are often called new generation polymers; they predict a great future as materials of special destination. The presence of channels and pores in dendrimer macromolecules allows them to be used for encapsulation and immobilization of guest low molecular weight molecules, including physiologically active ones. Such compositions, built according to the guest-host type, are promising for use in biology, medicine, pharmacology, cosmetics (Semchikov Yu. D. Dendrimers - a new class of polymers. Soros Educational Journal, 1998, Nbl2, pp. 45-51).

SUMMARY OF THE INVENTION

In a first aspect, the claimed invention relates to a new use of a dendrimer for enhancing the remineralizing effect of a calcium-containing dentifrice and oral cavity.

In a particular embodiment, the dendrimer may be gidroksidodetsilgidroksietiletilendiamin / methyl acrylate dendrimer, ethylene / methyl acrylate dendrimer, polyethylene glycol-222 pentaeritritiladipatsuktsinimidny dendrimer, polyethylene-5 pentaeritritildimetilolpropionat-2 dendrimer, polyethylene-5 pentaeritritildimetilolpropionat-3 dendrimer, polyethylene-5 pentaeritritildimetilolpropionat-4 dendrimer, polyethylene glycol -5 pentaerythrityl DMPA-2 caprate / caprylate dendrimer, sodium pentaerythrityl hydroxypropyliminodiacetate dendrimer, sodium trimethylolpropane hydroxypropyliminodiacetate dendrimer, trimethylolpropane hydroxypropyl-bnS-hydroxyethylamine dendrimer.

In a specific embodiment of the invention, the dendrimer in the calcium-containing dentifrice and oral cavity can be present in an amount from about 0.000001 wt. up to about 5% wt., preferably from about 0.00001% wt. up to about 4% wt., more preferably from about 0.0001% wt. up to about 3% wt., even more preferably from about 0.001% wt. up to about 2% wt., even more preferably from about 0.01% wt. up to about 1% wt., most preferably about 0.1% wt. The dendrimer in the calcium-containing dentifrice and oral cavity can be present in an amount of 0.000001 -5 wt%, preferably 0.00001-4 wt%, more preferably 0.0001 -3 wt%, even more preferably 0.001- 2% wt., Even more preferably 0.01-1% wt., Most preferably 0.1% wt.

In a specific embodiment, the calcium-containing dentifrice and oral cavity may contain hydroxyapatite, calcium citrate, phosphate calcium, calcium pyrophosphate, calcium glycerophosphate, calcium lactate, calcium chloride, calcium sulfate.

In a particular embodiment, the calcium-containing dentifrice and oral cavity can be a toothpaste. Moreover, the calcium-containing agent for the care of the teeth and the oral cavity can be a toothpaste in which the dendrimer is contained in an amount from about 0.000001 wt. up to about 5% wt., preferably from about 0.00001% wt. up to about 4% wt., more preferably from about 0.0001% wt. up to about 3% wt., even more preferably from about 0.001% wt. up to about 2% wt., even more preferably from about 0.01% wt. up to about 1% wt., most preferably about 0.1% wt. The calcium-containing dentifrice and oral cavity can be a toothpaste in which the dendrimer is contained in an amount of 0.000001 -5 wt%, preferably 0.00001-4 wt%, more preferably 0.0001 -3 wt%. , even more preferably 0.001-2% wt., even more preferably 0.01-1% wt., most preferably 0.1% wt.

In a specific embodiment, the calcium-containing dentifrice and oral cavity can be a dental and oral care gel. Moreover, the calcium-containing agent for the care of the teeth and the oral cavity can be a gel for the care of the teeth and the oral cavity, in which the dendrimer is contained in an amount of about 0.00001 wt. up to about 5% wt., preferably from about 0.0001% wt. up to about 4% wt., more preferably from about 0.001% wt. up to about 3% wt., even more preferably from about 0.01% wt. up to about 2% wt., even more preferably from about 0.1% wt. up to about 1% wt., most preferably about 0.5% wt. The calcium-containing dentifrice and oral cavity care gel may be a dental and oral care gel, in which the dendrimer is contained in an amount of 0.00001-5 wt%, preferably 0.0001-4 wt%, more preferably 0.001 - 3% wt., Even more preferably 0.01-2% wt., Even more preferably 0.1-1% wt., Most preferably 0.5% wt.

In a specific embodiment, the calcium-containing dentifrice and oral cavity can be a mouth and mouth rinse. Moreover, the calcium-containing agent for the care of the teeth and the oral cavity can be a rinse for the care of the teeth and the oral cavity, in which the dendrimer is contained in an amount from about 0.00001 wt. up to about 5% wt., preferably from about 0.0001% wt. up to about 4% wt., more preferably from about 0.001% wt. up to about 3% wt., even more preferably from about 0.01% wt. before about 2% wt., even more preferably from about 0.1% wt. up to about 1% wt., most preferably about 0.5% wt. The calcium-containing dentifrice and oral cavity can be a rinse for the care of the teeth and oral cavity, in which the dendrimer is contained in an amount of 0.00001-5% by weight, preferably 0.0001-4% by weight, more preferably 0.001- 3% wt., Even more preferably 0.01-2% wt., Even more preferably 0.1-1% wt., Most preferably 0.5% wt.

In a specific embodiment, the calcium-containing dentifrice and oral cavity can be a dental and oral care chewing gum, foam, serum, aerosol, oral strips, ointment, irrigator fluid, tooth powder.

In a second aspect, the invention relates to a novel use of a dendrimer for the manufacture of a calcium-containing dentifrice and oral care product, said dendrimer enhancing the remineralizing effect of the calcium-containing dentifrice and oral care product.

In a particular embodiment, the dendrimer may be gidroksidodetsilgidroksietiletilendiamin / methyl acrylate dendrimer, ethylene / methyl acrylate dendrimer, polyethylene glycol-222 pentaeritritiladipatsuktsinimidny dendrimer, polyethylene-5 pentaeritritildimetilolpropionat-2 dendrimer, polyethylene-5 pentaeritritildimetilolpropionat-3 dendrimer, polyethylene-5 pentaeritritildimetilolpropionat-4 dendrimer, polyethylene glycol -5 pentaerythrityl DMPA-2 caprate / caprylate dendrimer, sodium pentaerythrityl hydroxypropyliminodiacetate dendrimer, sodium trimethylolpropane hydroxypropyliminodiacetate dendrimer, trimethylolpropane hydroxypropyl-bms-hydroxyethylamine dendrimer.

In a specific embodiment of the invention, the dendrimer in the calcium-containing dentifrice and oral cavity can be present in an amount from about 0.000001 wt. up to about 5% wt., preferably from about 0.00001% wt. up to about 4% wt., more preferably from about 0.0001% wt. up to about 3% wt., even more preferably from about 0.001% wt. up to about 2% wt., even more preferably from about 0.01% wt. up to about 1% wt., most preferably about 0.1% wt. The dendrimer in the calcium-containing dentifrice and oral cavity can be contained in an amount of 0.000001 -5 wt%, preferably 0.00001-4 wt%, more preferably 0.0001 -3 wt%, even more preferably 0.001 - 2% wt., Even more preferably 0.01-1% wt., Most preferably 0.1% wt. In a specific embodiment, the calcium-containing dentifrice and oral cavity may contain hydroxyapatite, calcium citrate, calcium phosphate, calcium pyrophosphate, calcium glycerophosphate, calcium lactate, calcium chloride, calcium sulfate.

In a particular embodiment, the calcium-containing dentifrice and oral cavity can be a toothpaste. Moreover, the calcium-containing agent for the care of the teeth and the oral cavity can be a toothpaste in which the dendrimer is contained in an amount from about 0.000001 wt. up to about 5% wt., preferably from about 0.00001% wt. up to about 4% wt., more preferably from about 0.0001% wt. up to about 3% wt., even more preferably from about 0.001% wt. up to about 2% wt., even more preferably from about 0.01% wt. up to about 1% wt., most preferably about 0.1% wt. The calcium-containing dentifrice and oral cavity can be a toothpaste in which the dendrimer is contained in an amount of 0.000001-5 wt%, preferably 0.00001-4 wt%, more preferably 0.0001 -3 wt%. , even more preferably 0.001-2% wt., even more preferably 0.01-1% wt., most preferably 0.1% wt.

In a specific embodiment, the calcium-containing dentifrice and oral cavity can be a mouth and mouth rinse. Moreover, the calcium-containing agent for the care of the teeth and the oral cavity can be a rinse for the care of the teeth and the oral cavity, in which the dendrimer is contained in an amount from about 0.00001 wt. to about 5% wt., Preferably from about 0.0001% wt. up to about 4% wt., more preferably from about 0.001% wt. up to about 3% wt., even more preferably from about 0.01% wt. up to about 2% wt., even more preferably from about 0.1% wt. up to about 1% wt., most preferably about 0.5% wt. The calcium-containing dentifrice and oral cavity can be a rinse for the care of the teeth and mouth, in which the dendrimer is contained in an amount of 0.00001 -5 wt%, preferably 0.0001-4 wt%, more preferably 0.001- 3% wt., Even more preferably 0.01-2% wt., Even more preferably 0.1-1% wt., Most preferably 0.5% wt.

In a third aspect, the invention relates to a calcium-containing dentifrice and oral care product comprising a dendrimer.

In a specific embodiment of the invention, the dendrimer in the calcium-containing dentifrice and oral cavity can be present in an amount from about 0.000001 wt. up to about 5% wt., preferably from about 0.00001% wt. up to about 4% wt., more preferably from about 0.0001% wt. up to about 3% wt., even more preferably from about 0.001% wt. up to about 2% wt., even more preferably from about 0.01% wt. up to about 1% wt., most preferably about 0.1% wt. The dendrimer in the calcium-containing dentifrice and oral cavity may be present in an amount of 0.000001 -5 wt%, preferably 0.00001-4 wt%, more preferably 0.0001-3 wt%, even more preferably 0.001- 2% wt., Even more preferably 0.01-1% wt., Most preferably 0.1% wt. In a specific embodiment, the calcium-containing dentifrice and oral cavity may contain hydroxyapatite, calcium citrate, calcium phosphate, calcium pyrophosphate, calcium glycerophosphate, calcium lactate, calcium chloride, calcium sulfate.

In a particular embodiment, the calcium-containing dentifrice and oral cavity can be a toothpaste. Moreover, the calcium-containing agent for the care of the teeth and the oral cavity can be a toothpaste in which the dendrimer is contained in an amount from about 0.000001 wt. up to about 5% wt., preferably from about 0.00001% wt. up to about 4% wt., more preferably from about 0.0001% wt. up to about 3% wt., even more preferably from about 0.001% wt. up to about 2% wt., even more preferably from about 0.01% wt. up to about 1% wt., most preferably about 0.1% wt. The calcium-containing dentifrice and oral cavity can be a toothpaste in which the dendrimer is contained in an amount of 0.000001 -5 wt%, preferably 0.00001-4 wt%, more preferably 0.0001-3 wt%. , even more preferably 0.001-2% wt., even more preferably 0.01-1% wt., most preferably 0.1% wt.

In a specific embodiment, the calcium-containing dentifrice and oral cavity can be a mouth and mouth rinse. Moreover, the calcium-containing agent for the care of the teeth and the oral cavity can be a rinse for the care of the teeth and the oral cavity, in which the dendrimer is contained in an amount from about 0.00001 wt. to about 5% wt., Preferably from about 0.0001% wt. up to about 4% wt., more preferably from about 0.001% wt. up to about 3% wt., even more preferably from about 0.01% wt. up to about 2% wt., even more preferably from about 0.1% wt. up to about 1% wt., most preferably about 0.5% wt. The calcium-containing dentifrice and oral cavity can be a rinse for the care of the teeth and oral cavity, in which the dendrimer is contained in an amount of 0.00001-5% by weight, preferably 0.0001-4% by weight, more preferably 0.001- 3% wt., Even more preferably 0.01-2% wt., Even more preferably 0.1-1% wt., Most preferably 0.5% wt.

DETAILED DESCRIPTION OF THE INVENTION The aim of the research carried out by the authors was to develop innovative formulations for remineralization. It was revealed and experimentally confirmed the enhancement of the remineralizing effect of calcium-containing agents for the care of teeth and oral cavity when dendrimers are added to their composition.

A new application of a dendrimer for enhancing the remineralizing effect of a calcium-containing agent for the care of teeth and oral cavity is proposed; a new use of a dendrimer for the manufacture of a calcium-containing dentifrice and oral cavity, said dendrimer enhancing the remineralizing effect of the calcium-containing dentifrice and oral cavity; a calcium-containing dental and oral care product containing a dendrimer. One of ordinary skill in the art understands that a calcium-containing dentifrice and oral care product may be a composition such as a dentifrice and oral care composition or a product such as a dental and oral care product.

The dendrimer may be a gidroksidodetsilgidroksietiletilendiamin / dendrimer methyl acrylate, ethylene / methyl acrylate dendrimer, polyethylene glycol-222 pentaeritritiladipatsuktsinimidny dendrimer, polyethylene glycol-5-2 pentaeritritildimetilolpropionat dendrimer, polyethylene glycol-3-5 pentaeritritildimetilolpropionat dendrimer, polyethylene glycol-5-4 pentaeritritildimetilolpropionat dendrimer, polyethylene-5 pentaerythrityl DMPA-2 caprate / caprylate dendrimer, sodium pentaerythrityl hydroxypropyliminodiacetate dendrimer, sodium trimethylolpropane hydroxypropyliminodiacetate dendrimer, trimethylolpropane hydroxypropyl bis-hydroxyethylamine dendrimer. (ethylenediamine / methyl acrylate dendrimer; hydroxydodecyl hydroxyethyl ethylenediamine / methyl acrylate dendrimer; Polyethylene glycol -222 pentaerythrityl adipate-succinimide dendrimer; Polyethylene glycol -5 pentaerythrityl dimethylol propionylate ethylene-2 dendrimer5; 5 pentaerythrityl dimethylol propionate-4 dendrimer; Polyethylene glycol -5 pentaerythrityl dmpa-2 caprate / caprylate dendrimer; sodium pentaerythrityl hydroxypropyl iminodiacetate hydroxypropyl. Hydroxypropyl-hydroxypropyl-bis-propylamine; sodium trimethylolpropane hydroxypropyl-iminodiaxycetate dendrimer

More specifically, the ethylenediamine / methyl acrylate dendrimer is a multi-branched polymer formed by the sequential reaction of ethylenediamine with methyl acrylate. Hydroxydodecylhydroxyethylethylenediamine / methyl acrylate dendrimer is a multi-branched polymer formed by the sequential reaction of ethylenediamine with methyl acrylate, monoethanolamine and epoxydidecane. Polyethylene glycol (PEG) -222 The pentaerythrityl dipinate succinimide dendrimer is a multi-branched polymer formed by the sequential reaction of 222 moles of pentaerythritol ethoxylate with adipic anhydride and N-hydroxysuccinimide. Polyethylene glycol-5

Pentaerythrityl dimethylolpropionate-2-dendrimer is a multi-branched polymer formed by the sequential reaction of 5 moles of pentaerythritol ethoxylate with 2 molar series of dimethylpropionic acid.

Polyethylene glycol-5 Pentaerythrityl dimethylolpropionate-3-dendrimer is a multi-branched polymer formed by the sequential reaction of 5 moles of pentaerythritol ethoxylate with 3 molar series of dimethylpropionic acid.

Polyethylene glycol-5 Pentaerythrityl dimethylolpropionate-4-dendrimer is a multi-branched polymer formed by the sequential reaction of 5 mol of pentaerythritol ethoxylate with 4 molar series of dimethylpropionic acid.

Polyethylene glycol-5 Pentaerythrityl DMPA-2 (2,2-dimethoxy-1,2-diphenylacetophenone) caprate / caprylate dendrimer is a multi-branched polymer formed by the sequential reaction of 5 mol pentaerythritol ethoxylate with 2 molar series of dimethylpropionic acid esterified with caprylic acid and capric acid. Pentaerythritylhydroxypropylimino diacetate dendrimer sodium is the sodium salt of a multi-branched polymer formed by the sequential reaction of pentaerythritol with hydroxypropyliminodiacetic acid. The dendrimer of sodium trimethylolpropane hydroxypropyliminodiacetate is the sodium salt of a multi-branched polymer formed by the sequential reaction of trimethylolpropane with hydroxypropyliminodiacetic acid.

Trimethylolpropane hydroxypropyl bis-hydroxyethylamine dendrimer is a multi-branched polymer formed by the sequential reaction of trimethylolpropane with hydroxypropyl bis-hydroxyethylamine.

In certain embodiments of the invention, the dendrimer in the calcium-containing dentifrice and oral cavity can be present in an amount from about 0.000001 wt. up to about 5% wt., preferably from about 0.00001% wt. up to about 4% wt., more preferably from about 0.0001% wt. up to about 3% wt., even more preferably from about 0.001% wt. up to about 2% wt., even more preferably from about 0.01% wt. up to about 1% wt., most preferably about 0.1% wt. Such as about 0.000001 wt%, about 0.000005 wt%, about 0.00001 wt%, about 0.00005 wt%, about 0.0001 wt%, about 0.0005 wt%, about 0.001% by weight, about 0.005% by weight, about 0.01% by weight, about 0.05% by weight, about 0.1% by weight, about 0.5% by weight, about 1.0% by weight ., about 1.5% wt., about 2.0% wt., about 2.5% wt., about 3.0% wt., about 3.5% wt., about 4.0% wt., about 4.5% wt., about 5.0% wt. Alternatively, the dendrimer in the calcium-containing dentifrice and oral cavity can be contained in an amount of 0.000001 wt%, 0.000005 wt%, 0.00001 wt%, 0.00005 wt%, 0.0001 wt%. , 0.0005% wt., 0.001% wt., 0.005% wt., 0.01% wt., 0.05% wt., 0.1% wt., 0.5% wt., 1.0% wt., 1.5% wt., 2.0% wt., 2.5% wt., 3.0% wt., 3.5% wt., 4.0% wt., 4.5% wt. ., 5.0% wt.

In a particular embodiment, the calcium-containing dentifrice and oral cavity may contain any acceptable calcium compound approved for use in dentifrice and oral care products, for example selected from the group consisting of or consisting of: hydroxyapatite, calcium citrate, calcium phosphate, calcium pyrophosphate, calcium glycerophosphate, calcium lactate, calcium chloride, calcium sulfate.

In a particular embodiment of the invention, the calcium-containing dentifrice and oral cavity can be of any suitable form used for dental and oral care, for example selected from the group consisting of or consisting of: toothpaste, gel for dentifrice and oral cavity mouth, rinse, chewing gum for dental and oral cavity care, foam, serum, aerosol, oral strips, ointment, liquid for irrigators, tooth powder.

EXPERIMENTAL PART

Example 1.

The aim of a randomized study was to establish the enhancement of the remineralizing effect of a calcium-containing toothpaste containing a dendrimer. The study involved men and women aged 18-45 years without chronic diseases. A total of 60 people participated in the study, 20 subjects each in the study groups and the comparison group. In the study group, subjects used a toothpaste containing hydroxyapatite with a dendrimer included (Group 1), in the comparison group, subjects used a toothpaste containing hydroxyapatite without a dendrimer (Group 2). The control group used a toothpaste free of hydroxyapatite and dendrimer (group 3).

In the experimental groups with the participation of patients, compositions were used that, as active ingredients, included the claimed complex containing a dendrimer - 0.00001% wt., Dry amorphous hydroxyapatite - 0.5% wt.

Table No 1. Study groups

The study participants used the toothpaste 2 times a day for 28 days.

The TER-test and KOSRE-test (clinical determination of the rate of enamel remineralization) were used as parameters for assessing the remineralizing effect of the drugs. Tests were performed at visits 1, 2, 3 and 4.

For the TER test (on visits 1, 2, 3, and 4), the vestibular surface of one of the upper central incisors was cleaned from plaque using a cotton ball soaked in hydrogen peroxide solution. The tooth cavity was dried with a cotton ball. The tooth was isolated from saliva with cotton rolls. To the center of the vestibular surface of the tooth A drop of 1% HC1 solution with a diameter of 1.5-2 mm was applied with a micropipette. After 5 seconds, the drop was washed off with distilled water. The tooth surface was dried with a cotton ball. 1 drop of 1% methylene blue solution was applied to the area of enamel that had been etched.

The dye was immediately removed with a dry cotton ball in one motion, pressing the ball tightly to the tooth surface.

In daylight, the color of the patch was compared with the shades of a standard 10-point scale. The acid resistance of the enamel was evaluated in points from 1 to 10 (from pale blue to dark blue).

According to the result obtained, the patient was classified into one of 4 dispensary groups:

1 gr. - 1-3 points - high acid resistance of the enamel.

2 gr. - 4-5 points - moderate acid resistance of the enamel.

3 gr. - 6-7 points - low acid resistance of the enamel.

4 gr. - More than 7 points - very low acid resistance of the enamel.

Caries risk assessment by TER test:

- 1 gr. according to FER - high resistance to caries, patients do not need active measures, hygienic oral care is required.

- 2 gr. according to fuel and energy resources - single carious lesions are expected, traditional preventive measures (local and general) are carried out once a year.

- 3-4 gr. according to FER - a high and very high risk of dental caries, preventive measures (local and general) are carried out 2-3 times a year.

Each of the subjects underwent KOSRE-test within 2 weeks, 4 weeks. As a demineralizing agent, a hydrochloric acid buffer solution (pH - 0, 3-0, 6) is used, consisting of 1N HC1 and 1N KC1. To stain the demineralized enamel area, a 2% solution of methylene blue is used. For the test, the working field is isolated, the vestibular surface of the central incisor is cleaned of plaque and dried. A drop of hydrochloric acid buffer solution (pH - 0.3-0.6), consisting of 1N HC1 and 1N KC1, is applied to the enamel surface with a glass rod, the drop diameter is about 2 mm. After 1 min, the drop is removed with a cotton swab and the etched area of the enamel is stained for the same time with a 2% aqueous solution of methylene blue. The staining of the etched enamel area is repeated at daily intervals until it loses its ability to stain. Thus, about the remineralizing ability of saliva judged by the period of time required for the complete restoration of the enamel structure. For people with a good KOSRE test, this figure does not exceed 3 days. For all quantitative data, the group arithmetic mean (M), median (Me), standard deviation (SD) and standard error of the mean (SEM), interquartile ranges, 90% CI were calculated. The results were processed using the IBM SPSS Statistics 22.0 software (StatSoft, Russia). The likelihood of differences in mean indices in the groups was determined using the Mann-Whitney test. Differences were considered significant at a significance level of p <0.05.

Results:

In the Nsl group, TEP at the beginning of the study was 3.0 ± 0.1, in the N ° 2 group - 3.0 ± 0.2, in the N ° 3 group - 3.0 ± 0.1. The differences between groups were statistically significant (p = p = 0.0005). After 1 month from the beginning of the study, the average TEP value in group 1 was 2.5 ± 0.1, in group 22.8 ± 0.1, in group 3 2.9 ± 0.2; differences between groups were statistically significant (p = 0.0001). The performed test showed an increase in the remineralizing effect of the composition containing dendrimer and hydroxyapatite 5 times compared to the control, and 2.5 times compared with the group N ° 2 containing only hydroxyapatite.

In the Nsl group before the study, the KOSRE test was 2.8 ± 0.04, in the N ° 2 group - 2.9 ± 0.05, in the No. 3 group - 2.7 ± 0.05. The differences between the groups were statistically significant (p = 0.005). After 1 month from the beginning of the study, the average value of the KOSRE test in the groups was 1.8 ± 0.01, 2.3 ± 0.01, 2.4 ± 0.02. The differences between groups were statistically significant (p = 0.0001). At the end of the study, the KOSRE-test decreased in all studied groups, and in control group 3 the decrease was insignificant. In group 1, the KOSRE test decreased by 3 times compared with the control group, in group 2, 2 times compared with the control.

Thus, the use of a calcium-containing toothpaste with the inclusion of a dendrimer, already with such a low content as 0.00001% by weight, leads to an increase in enamel remineralization by 5 times, and a synergistic effect of calcium salt (calcium ion) and dendrimer was shown. This effect was significantly expressed in comparison with the use of the toothpaste without the inclusion of the composition.

The use of a calcium-containing toothpaste with the inclusion of a dendrimer in an amount of 0.00001% wt., Leads to an increase in the rate of enamel remineralization of enamel remineralization by 3 times due to the reliable synergistic action of the components in the composition. Example 2.

The aim of the randomized study was also to determine the enhancement of the remineralizing effect of an enamel gel containing a dendrimer. The study involved men and women aged 18-45 years without chronic diseases. A total of 40 people participated in the study, 20 subjects each in the study group and the comparison group. In the study group, subjects used a calcium-containing gel, with the inclusion of a dendrimer (group 1), in the comparison group, subjects used a gel of the same composition, but without a dendrimer (group 2).

In the experimental groups with the participation of patients, compositions were used, which, as active ingredients, included the claimed complex containing a dendrimer - 0.00001% wt., Calcium glycerophosphate - 0.2% wt.

Table N ° 2. Study groups

After brushing their teeth with fluoride-free toothpaste, participants applied the gel to their teeth using a tip and spread their tongue over the entire enamel surface. Do not rinse with water after use and do not eat for 40 minutes. The total gel time was 28 days with one use per day.

The parameter for assessing the remineralizing effect of drugs was the TER test. The procedure was performed at visits 1, 2, 3 and 4. Additionally, the Schiff index was assessed to determine the degree of desensitization before and after using the gel.

For the TER test, the vestibular surface of one of the upper central incisors was cleaned of plaque using a cotton ball moistened with hydrogen peroxide solution. The tooth was dried with a cotton ball. The tooth was isolated from saliva with cotton rolls. A drop of 1% HC1 solution 1.5-2 mm in diameter was applied to the center of the vestibular surface of the tooth with a micropipette. After 5 seconds, the drop was washed off with distilled water. The tooth surface was dried with a cotton ball. 1 drop of 1% methylene blue solution was applied to the area of enamel that had been etched. The dye was immediately removed with a dry cotton ball in one motion, pressing the ball tightly to the tooth surface.

1 gr. - 1-3 points - high acid resistance of the enamel.

2 gr. - 4-5 points - moderate acid resistance of the enamel.

3 gr. - 6-7 points - low acid resistance of the enamel.

4 gr. - More than 7 points - very low acid resistance of the enamel.

Caries risk assessment by TER test:

• 1 gr. according to FER - high resistance to caries, patients do not need active measures, hygienic oral care is required.

• 2 gr. according to fuel and energy resources - single carious lesions are expected, traditional preventive measures (local and general) are carried out once a year.

• 3-4 gr. according to FER - a high and very high risk of dental caries, preventive measures (local and general) are carried out 2-3 times a year.

The effectiveness of the gel treatment was assessed by the results of determining the Schiff index, based on the determination of the tooth sensitivity threshold using an air jet according to Schiff in all groups. The Schiff air test is carried out as follows: air from a pistol of the dental unit is supplied perpendicular to the cervical surface of the tooth from a distance of 1 cm for a second (under a pressure of 40 - 60 psi) at a temperature of 21 degrees Celsius (Fig. 9). Tooth sensitivity is assessed using the following criteria: 0 - no response; 1 - a feeling of discomfort, but the patient does not insist on stopping the test; 2 - discomfort accompanied by a request to stop the test; 3 - severe pain reaction with pronounced motor responses aimed at immediate termination of the test.

The determination of the Schiff index was carried out in the patients of the groups after 2 weeks and 4 weeks.

For all quantitative data, the group arithmetic mean (M), median (Me), standard deviation (SD) and standard error of the mean (SEM), interquartile ranges, 90% CI were calculated. The results were processed using the IBM SPSS Statistics 22.0 software (StatSoft, Russia). Probability of differences in average in groups was determined using the Mann-Whitney test. Differences were considered significant at a significance level of p <0.05.

Results:

As a result of evaluating the dynamics of acid-resistant ™ enamel in patients of all groups, it was found that with daily use of the gel with dendrimers for a month, the acid resistance of the enamel of the teeth increased. Thus, in the N ° l group, TEP at the beginning of the study was 3.0 ± 0.1, in the Ne 2 group - 2.8 ± 0.2. The differences between groups were statistically significant (p = p = 0.0004). After 1 month from the beginning of the study, the average TEP value in group 1 was 1.8 ± 0.1, and in group 2, 2.6 ± 0.1; differences between groups were statistically significant (p = 0.0001). The test performed showed an increase in the remineralizing effect of the composition containing the dendrimer in 6 in comparison with the control.

The Schiff index before the start of treatment was in the group N ° 1-2.9 POD, in the group N ° 2 - 2.7 P 0.1. The differences between the groups were statistically significant (p = 0.005). After 2 weeks, the Schiff index in group Ns 1-2,000.1, in group N ° 2 - 2.2 Ώ 0.2. The Schiff index after 1 month was Le1-1, ZP0.1, in group N ° 2 - 2.0D0.01. Differences between groups at 1 month were statistically significant (p = 0.0001). In all groups, the sensitivity decreased, and in group 1, which used a toothpaste with dendrimers and calcium glycerophosphate, the sensitivity for 4 weeks of use decreased by 2 times due to the reliable synergistic action of the components in the composition.

Thus, the use of a calcium-containing gel with the inclusion of a dendrimer in an amount of 0.00001% wt. leads to an increase in enamel remineralization by 6 times and a decrease in sensitivity by 2 times. Moreover, this effect was significantly expressed in comparison with the use of the gel without the inclusion of a dendrimer in the composition, which indicates the synergism of the components that make up the complex.

Example 3.

The aim of the laboratory study was to establish the enhancement of the remineralizing effect of an enamel gel containing a dendrimer in comparison with existing products containing proven remineralizing compositions.

In the present in vitro study, Raman fluorescence spectroscopy (after hygienic cleaning with professional toothpaste) was carried out on 20 model test objects of teeth (incisors of the lower jaw), removed for clinical indications, using a laser hardware-software complex with a wavelength probe radiation 532 nm. Of these: 5 model test objects of the teeth were placed in a 10% suspension of nano-HAP for 1 minute for 21 days (the period recommended for remineralizing therapy); 5 test objects were cleaned with a paste containing nano-HAP daily for 21 days in the morning and evening; 5 test objects for 21 days (once a day) applied a gel containing nano-HAP in complex with soluble calcium in one preparation; control group - 5 test objects that were in deionized water for 21 days. Measurements of the Raman-fluorescent characteristics of dental hard tissues were carried out after 21 days. Repeated measurements in all groups were carried out after 14 days to determine the duration of the preservation of the effect of tooth enamel mineralization. For a quantitative assessment of the spectral intensity of Raman radiation (in relative units M avg.), The spectral indices at the maximum and minimum of its power and the indices of fluorescence intensity (M avg) were measured. Registration and software processing of the research results took 2 minutes. The results (M cf.) research are presented in the form of figures and tables.

For all quantitative data, the group arithmetic mean (M), median (Me), standard deviation (SD) and standard error of the mean (SEM), interquartile ranges, 90% CI were calculated. The results were processed using the IBM SPSS Statistics 22.0 software (StatSoft, Russia). The likelihood of differences in mean indices in the groups was determined using the Mann-Whitney test. Differences were considered significant at a significance level of p <0.05.

Results:

The experimental data are presented in Table N ° 3.

Table N ° 3. Average spectral characteristics of enamel before and after remineralizing therapy.

As a result of evaluating the remineralizing effect, it was found that after a course of remineralizing therapy for 21 days with various remineralizing drugs, the intensity of the Raman line of hydroxyapatite (p = 0.004) significantly increased in all test objects (i.e., an increase in the concentration of hydroxyapatite in the tooth enamel ) in relation to control. The best indicators of remineralizing therapy for 21 days were obtained for a gel containing dendrimers in a complex with soluble calcium. After the test objects were in deionized water for a month, the intensity of the Raman peak decreased, but did not reach the initial limit.

Thus, the use of a calcium-containing gel with the inclusion of a dendrimer in an amount of 0.00001% wt. leads to a significant increase in enamel remineralization in comparison with known products containing hydroxyapatite as a component for enamel strengthening.

Example 4.

The aim of the study was to establish changes in the concentration of sodium, potassium, calcium, chlorine, phosphate ions in salivary fluid in the intervals between meals when using a calcium-containing toothpaste containing a dendrimer. The study involved men and women aged 18-45 years without chronic diseases. A total of 40 people participated in the study, 40 subjects each in the study group and the comparison group. In the study group, subjects used dendrimer-containing calcium toothpaste (group 1), in the comparison group, subjects used a dendrimer-containing calcium toothpaste of the same composition, but no dendrimer (group 2). Participants in the study brushed their teeth with toothpaste 2 times a day, morning and evening, for 2 weeks. For the study, salivary fluid was collected before applying the toothpaste and after four weeks of use.

After applying the toothpaste in group 1, there was a significant increase in the concentration of calcium ions and the normalization of the concentration of phosphate ions and sodium ions. Thus, the use of toothpaste allows an increase in the concentration of calcium ions, which is a positive factor for the remineralization of tooth enamel. The concentration of other ions either remains within normal limits, or normalizes (phosphate ions and sodium ions), which helps to maintain a neutral pH level and creates optimal conditions for remineralization of enamel (Table N ° 4).

Table Dz4. Indicators of the mineral composition of salivary fluid.

Thus, a composition based on a dendrimer and calcium salts helps to increase the concentration of calcium ions and normalize phosphate ions, and, therefore, can be used to enhance the remineralization of enamel and maintain a neutral pH in the oral cavity.

Example 5.

The aim of a randomized study was to establish the enhancement of the remineralizing effect of a calcium-containing toothpaste containing various dendrimers. The study involved men and women aged 18-45 years without chronic diseases. A total of 100 people participated in the study, 20 subjects each in the study groups and the comparison group. In the study group, subjects used a toothpaste containing hydroxyapatite containing hydroxydodecylhydroxyethylethylenediamine / methyl acrylate dendrimer (group 1), compared with a group whose subjects used a toothpaste containing hydroxyapatite with polyethylene glycol-5 pentaerythrityldimethyl-2-pastendrimer-arylpropion group containing hydroxyapatite with polyethylene glycol-5 pentaerythrityl DMPA-2 caprate / caprylate dendrimer (group 3). In the comparison group, subjects used hydroxyapatite toothpaste without the inclusion of dendrimers (group 2). The control group used a toothpaste free of hydroxyapatite and dendrimer (group 3).

Table Ns5. Study groups

The study participants used the toothpaste 2 times a day for

28 days. The TER-test and KOSRE-test (clinical determination of the rate of enamel remineralization) were used as parameters for assessing the remineralizing effect of the drugs. Tests were performed at visits 1, 2, 3 and 4.

For the TER test (on visits 1, 2, 3, and 4), the vestibular surface of one of the upper central incisors was cleaned from plaque using a cotton ball soaked in hydrogen peroxide solution. The tooth cavity was dried with a cotton ball. The tooth was isolated from saliva with cotton rolls. A drop of 1% HC1 solution 1.5-2 mm in diameter was applied to the center of the vestibular surface of the tooth with a micropipette. After 5 seconds, the drop was washed off with distilled water. The tooth surface was dried with a cotton ball. 1 drop of 1% methylene blue solution was applied to the area of enamel that had been etched.

1 gr. - 1-3 points - high acid resistance of the enamel.

2 gr. - 4-5 points - moderate acid resistance of the enamel.

3 gr. - 6-7 points - low acid resistance of the enamel.

4 gr. - More than 7 points - very low acid resistance of the enamel.

Caries risk assessment by TER test:

Each of the subjects underwent KOSRE-test within 2 weeks, 4 weeks. As a demineralizing agent, a hydrochloric acid buffer solution (pH - 0, 3-0, 6) is used, consisting of 1H HC1 and 1N KC1. To stain the demineralized enamel area, a 2% solution of methylene blue is used. For the test, the working field is isolated, the vestibular surface of the central incisor is cleaned of plaque and dried. On the enamel surface a drop of hydrochloric acid buffer solution (pH - 0.3-0.6), consisting of 1N HC1 and 1N KC1, is applied with a glass rod, the diameter of the drop is about 2 mm. After 1 min, the drop is removed with a cotton swab and the etched area of the enamel is stained for the same time with a 2% aqueous solution of methylene blue. The staining of the etched enamel area is repeated at daily intervals until it loses its ability to stain. Thus, the remineralizing ability of saliva is judged by the period of time required for the complete restoration of the enamel structure. For people with a good KOSRE test, this figure does not exceed 3 days. For all quantitative data, the group arithmetic mean (M), median (Me), standard deviation (SD) and standard error of the mean (SEM), interquartile ranges, 90% CI were calculated. The results were processed using the IBM SPSS Statistics 22.0 software (StatSoft, Russia). The likelihood of differences in mean indices in the groups was determined using the Mann-Whitney test. Differences were considered significant at a significance level of p <0.05.

Results:

In the Nsl group, TEP at the beginning of the study was 3.0 ± 0.1, in the Ns 2 group - 3.1 ± 0.2, in the N ° 3 group - 3.0 ± 0.2, in the N ° 4 group - 2.9 ± 0.2, for group No. 5 3.1 ± 0.1. The differences between groups were statistically significant (p = p = 0.0005). After 1 month from the start of the study, the average TEP value in group 1 was 2.5 ± 0.1, in group 2 2.4 ± 0.1, in group 3 2.4 ± 0.1, in group 4 2.8 ± 0.1, in group 5 2.9 ± 0.2; differences between groups were statistically significant (p = 0.0001). The test showed an increase in the remineralizing effect of a composition containing a dendrimer (hydroxydodecylhydroxyethylethylenediamine / methyl acrylate dendrimer or polyethylene glycol-5 pentaerythrityl dimethylolpropionate-2 dendrimer or polyethylene glycol-5 pentaerythrityl DMPA-2 caprimer / and caprylate in the control dendrimer 2.5 times compared to group No. 4 containing hydroxyapatite only.

In group N "1 before the study, the KOSRE test was 2.80 ± 0.04, in group N ° 2 - 2.90 ± 0.05, in group N ° 3 - 2.87 ± 0.05, in group N ° 4 - 2.92 ± 0.05, in group s 5 2.71 ± 0.05. The differences between the groups were statistically significant (p = 0.005). After 1 month from the beginning of the study, the average value of the KOSRE test in five groups was 1.8 ± 0.01, 2.4 ± 0.03, 2.4 ± 0.02, 2.3 ± 0.01, 2.4 ± 0.02, respectively. The differences between groups were statistically significant (p = 0.0001). At the end of the study, the KOSRE-test decreased in all studied groups, and in the control group 5 the decrease was insignificant. In group 1, the KOSRE test decreased 3.5 times compared with the control group, in group 2 - 3 times compared to the control, in group 3 - 3.2 times compared to the control, in group 4 - 2 times compared to the control.

Thus, the use of a calcium-containing toothpaste with the inclusion of a dendrimer in an amount of 0.00001% wt. leads to an increase in enamel remineralization by 5 times, and the synergistic effect of calcium salt and dendrimer has been proven. This effect was significantly pronounced compared to using the toothpaste without the inclusion of the composition.

The use of a calcium-containing toothpaste with the inclusion of a dendrimer in an amount of 0.00001% wt. leads to an increase in the rate of enamel remineralization of enamel remineralization by 3 times due to the reliable synergistic action of the components in the composition.

Claims

CLAIM

1. Application of a dendrimer to enhance the remineralizing effect of a calcium-containing product for the care of teeth and oral cavity.

2. The use according to Claim. 1, where the dendrimer is gidroksidodetsilgidroksietiletilendiamin / dendrimer methyl acrylate, ethylene / methyl acrylate dendrimer, polyethylene glycol-222 pentaeritritiladipatsuktsinimidny dendrimer, polyethylene glycol-5-2 pentaeritritildimetilolpropionat dendrimer, polyethylene glycol-3-5 pentaeritritildimetilolpropionat dendrimer, polyethylene glycol-5-4 pentaeritritildimetilolpropionat dendrimer, polyethylene glycol-5 pentaerythrityl DMPA-2 caprate / caprylate dendrimer, sodium pentaerythrityl hydroxypropyliminodiacetate dendrimer, sodium trimethylolpropanhydroxypropylimino diacetate dendrimer, trimethylolpropane hydroxypropyl-bms-hydroxyethylene hydroxyethylene.

3. The use according to p. 1 or p. 2, where the dendrimer in the calcium-containing means for caring for teeth and oral cavity is contained in an amount of from about 0.000001% wt. up to about 5% wt., preferably from about 0.00001% wt. up to about 4% wt., more preferably from about 0.0001% wt. up to about 3% wt., even more preferably from about 0.001% wt. up to about 2% wt., even more preferably from about 0.01% wt. up to about 1% wt., most preferably about 0.1% wt.

4. Use according to claim 3, wherein the dendrimer in the calcium-containing dentifrice and oral cavity is contained in an amount of 0.000001-5% by weight, preferably 0.00001-4% by weight, more preferably 0.0001 -3% wt., even more preferably 0.001-2% wt., even more preferably 0.01-1% wt., most preferably 0.1% wt.

5. Use according to claim 1, wherein the calcium-containing dental and oral care product contains hydroxyapatite, calcium citrate, calcium phosphate, calcium pyrophosphate, calcium glycerophosphate, calcium lactate, calcium chloride, calcium sulfate.

6. Use according to claim 1, wherein the calcium-containing dentifrice and oral cavity is a toothpaste.

7. The use according to p. 6, where the calcium-containing agent for the care of teeth and oral cavity is a toothpaste, in which the dendrimer is contained in an amount from about 0.000001% wt. up to about 5% wt., preferably from about 0.00001% wt. up to about 4% wt., more preferably from about 0.0001% wt. up to about 3% wt., even more preferably from about 0.001% wt. up to about 2% wt., even more preferably from about 0.01% wt. up to about 1% wt., most preferably about 0.1% wt.

8. Use according to claim 7, wherein the calcium-containing dentifrice and oral cavity care product is a toothpaste in which the dendrimer is contained in an amount of 0.000001-5 wt%, preferably 0.00001-4 wt%, more preferably 0.0001-3 wt%, even more preferably 0.001-2 wt%, even more preferably 0.01-1 wt%, most preferably 0.1 wt%.

9. Use according to claim 1, wherein the calcium-containing dental and oral care product is a dental and oral care gel.

10. The use according to p. 9, where the calcium-containing means for caring for teeth and oral cavity is a gel for caring for teeth and oral cavity, in which the dendrimer is contained in an amount of from about 0.00001% wt. up to about 5% wt., preferably from about 0.0001% wt. up to about 4% wt., more preferably from about 0.001% wt. up to about 3% wt., even more preferably from about 0.01% wt. up to about 2% wt., even more preferably from about 0.1% wt. up to about 1% wt., most preferably about 0.5% wt.

11. Use according to claim 10, wherein the calcium-containing dentifrice and oral cavity care gel is a dental and oral care gel, wherein the dendrimer is contained in an amount of 0.00001 -5% by weight, preferably 0.0001-4 % wt., more preferably 0.001 -3% wt., even more preferably 0.01-2% wt., even more preferably 0.1-1% wt., most preferably 0.5% wt.

12. The use according to claim 1, wherein the calcium-containing dentifrice and oral cavity care product is a rinse for the care of the teeth and oral cavity.

13. The use according to p. 12, where the calcium-containing agent for the care of teeth and oral cavity is a rinse for the care of teeth and oral cavity, in which the dendrimer is contained in an amount from about 0.00001% wt. up to about 5% wt., preferably from about 0.0001% wt. up to about 4% wt., more preferably from about 0.001% wt. up to about 3% wt., even more preferably from about 0.01% wt. up to about 2% wt., even more preferably from about 0.1% wt. up to about 1% wt., most preferably about 0.5% wt.

14. Use according to claim 13, wherein the calcium-containing dentifrice and oral cavity care product is a rinse for the care of teeth and oral cavity, in which the dendrimer is contained in an amount of 0.00001-5% by weight, preferably 0.0001-4 % wt., more preferably 0.001 -3% wt., even more preferably 0.01-2% wt., even more preferably 0.1-1% wt., most preferably 0.5% wt.

15. Use according to claim 1, wherein the calcium-containing dental and oral care product is a chewing gum for dental and oral care, foam, serum, aerosol, oral strips, ointment, irrigator fluid, tooth powder.

16. Use of a dendrimer for the manufacture of a calcium-containing dentifrice and oral cavity, wherein said dendrimer enhances the remineralizing effect of the calcium-containing dentifrice and oral cavity.

17. The use of claim. 16 wherein the dendrimer is gidroksidodetsilgidroksietiletilendiamin / dendrimer methyl acrylate, ethylene / methyl acrylate dendrimer, polyethylene glycol-222 pentaeritritiladipatsuktsinimidny dendrimer, polyethylene glycol-5-2 pentaeritritildimetilolpropionat dendrimer, polyethylene glycol-3-5 pentaeritritildimetilolpropionat dendrimer, polyethylene glycol-5-4 pentaeritritildimetilolpropionat dendrimer, polyethylene glycol-5 pentaerythrityl DMPA-2 caprate / caprylate dendrimer, sodium pentaerythrityl hydroxypropyliminodiacetate dendrimer, sodium trimethylolpropanhydroxypropylimino diacetate dendrimer, trimethylolpropane hydroxypropyl-bms-hydroxyethylene hydroxyethylene.

18. The use according to p. 16 or p. 17, where the dendrimer in the calcium-containing means for caring for teeth and oral cavity is contained in an amount of from about 0.000001% wt. up to about 5% wt., preferably from about 0.00001% wt. up to about 4% wt., more preferably from about 0.0001% wt. up to about 3% wt., even more preferably from about 0.001% wt. up to about 2% wt., even more preferably from about 0.01% wt. up to about 1% wt., most preferably about 0.1% wt.

19. Use according to claim 18, wherein the dendrimer in the calcium-containing dentifrice and oral cavity is contained in an amount of 0.000001-5% by weight, preferably 0.00001-4% by weight, more preferably 0.0001 -3% wt., even more preferably 0.001-2 wt.%, even more preferably 0.01-1 wt.%, most preferably 0.1 wt.%

20. Use according to claim 16, wherein the calcium-containing dentifrice and oral cavity care product contains hydroxyapatite, calcium citrate, calcium phosphate, calcium pyrophosphate, calcium glycerophosphate, calcium lactate, calcium chloride, calcium sulfate.

21. The use of claim 16, wherein the calcium-containing dentifrice and oral cavity is a toothpaste.

22. The use according to claim 21, where the calcium-containing agent for the care of teeth and oral cavity is a toothpaste, in which the dendrimer is contained in an amount from about 0.000001% wt. up to about 5% wt., preferably from about 0.00001% wt. up to about 4% wt., more preferably from about 0.0001% wt. up to about 3% wt., even more preferably from about 0.001% wt. up to about 2% wt., even more preferably from about 0.01% wt. up to about 1% wt., most preferably about 0.1% wt.

23. Use according to claim 22, wherein the calcium-containing dentifrice and oral cavity is a toothpaste in which the dendrimer is contained in an amount of 0.000001 -5 wt%, preferably 0.00001-4 wt%, more preferably 0.0001-3 wt%, even more preferably 0.001-2 wt%, even more preferably 0.01-1 wt%, most preferably 0.1 wt%.

24. The use of claim 16, wherein the calcium-containing dentifrice and oral cavity care product is a dental and oral care gel.

25. The use according to p. 24, where the calcium-containing means for caring for teeth and oral cavity is a gel for caring for teeth and oral cavity, in which the dendrimer is contained in an amount of from about 0.00001% wt. up to about 5% wt., preferably from about 0.0001% wt. up to about 4% wt., more preferably from about 0.001% wt. up to about 3% wt., even more preferably from about 0.01% wt. up to about 2% wt., even more preferably from about 0.1% wt. up to about 1% wt., most preferably about 0.5% wt.

26. Use according to claim 25, wherein the calcium-containing dentifrice and oral cavity care gel is a dental and oral care gel, wherein the dendrimer is contained in an amount of 0.00001 -5 wt%, preferably 0.0001-4 % wt., more preferably 0.001 -3% wt., even more preferably 0.01-2% wt., even more preferably 0.1-1% wt., most preferably 0.5% wt.

27. The use according to claim 16, wherein the calcium-containing dentifrice and oral cavity is a rinse for the care of teeth and oral cavity.

28. The use according to p. 27, where the calcium-containing agent for the care of teeth and oral cavity is a rinse for the care of teeth and oral cavity, in which the dendrimer is contained in an amount of from about 0.00001% wt. up to about 5% wt., preferably from about 0.0001% wt. up to about 4% wt., more preferably from about 0.001% wt. up to about 3% wt., even more preferably from about 0.01% wt. up to about 2% wt., even more preferably from about 0.1% wt. up to about 1% wt., most preferably about 0.5% wt.

29. Use according to claim 28, wherein the calcium-containing dentifrice and oral cavity care product is a rinse for the care of teeth and oral cavity, in which the dendrimer is contained in an amount of 0.00001-5% by weight, preferably 0.0001-4 % wt., more preferably 0.001-3 wt%, even more preferably 0.01-2 wt%, even more preferably 0.1-1 wt%, most preferably 0.5 wt%.

30. Use according to claim 16, wherein the calcium-containing dentifrice and oral cavity care product is a dental and oral care chewing gum, foam, serum, aerosol, oral strips, ointment, irrigator fluid, tooth powder.

31. Remineralizing calcium-containing product for the care of teeth and oral cavity, containing a dendrimer.

32. The compound according to claim. 31 wherein the dendrimer is gidroksidodetsilgidroksietiletilendiamin / dendrimer methyl acrylate, ethylene / methyl acrylate dendrimer, polyethylene glycol-222 pentaeritritiladipatsuktsinimidny dendrimer, polyethylene glycol-5-2 pentaeritritildimetilolpropionat dendrimer, polyethylene glycol-3-5 pentaeritritildimetilolpropionat dendrimer, polyethylene glycol-5-4 pentaeritritildimetilolpropionat dendrimer, polyethylene glycol-5 pentaerythrityl DMPA-2 caprate / caprylate dendrimer, sodium pentaerythritylhydroxypropyliminodiacetate dendrimer, sodium trimethylolpropanhydroxypropyliminodiacetate dendrimer, trimethylolpropane hydroxypropyl-bms-hydroxyethylene dyroxyethylene.

33. The tool according to p. 31 or p. 32, where the dendrimer in the calcium-containing means for caring for the teeth and the oral cavity is contained in an amount of from about 0.000001% wt. up to about 5% wt., preferably from about 0.00001% wt. up to about 4% wt., more preferably from about 0.0001% wt. up to about 3% wt., even more preferably from about 0.001% wt. up to about 2% wt., even more preferably from about 0.01% wt. up to about 1% wt., most preferably about 0.1% wt.

34. The agent according to claim 33, wherein the dendrimer in the calcium-containing dentifrice and oral cavity is contained in an amount of 0.000001-5 wt%, preferably 0.00001-4 wt%, more preferably 0.0001-3% wt., even more preferably 0.001-2% wt., even more preferably 0.01-1% wt., most preferably 0.1% wt.

35. The agent according to claim 31, wherein the calcium-containing agent for dental and oral cavity care contains hydroxyapatite, calcium citrate, calcium phosphate, calcium pyrophosphate, calcium glycerophosphate, calcium lactate, calcium chloride, calcium sulfate.

36. An agent according to claim 31, wherein the calcium-containing dentifrice and oral cavity care agent is a toothpaste.

37. The tool according to p. 36, where the calcium-containing agent for the care of teeth and oral cavity is a toothpaste, in which the dendrimer is contained in an amount from about 0.000001% wt. up to about 5% wt., preferably from about 0.00001% wt. up to about 4% wt., more preferably from about 0.0001% wt. up to about 3% wt., even more preferably from about 0.001% wt. up to about 2% wt., even more preferably from about 0.01% wt. up to about 1% wt., most preferably about 0.1% wt.

38. The agent according to claim 37, wherein the calcium-containing dentifrice and oral cavity care agent is a toothpaste in which the dendrimer is contained in an amount of 0.000001-5 wt%, preferably 0.00001-4 wt%, more preferably 0.0001-3% wt., Even more preferably 0.001-2% wt., Even more preferably 0.01-1% wt., Most preferably 0.1% wt.

39. An agent according to claim 31, wherein the calcium-containing dentifrice and oral care agent is a dental and oral care gel.

40. The tool according to p. 39, where the calcium-containing means for caring for teeth and oral cavity is a gel for caring for teeth and oral cavity, in which the dendrimer is contained in an amount from about 0.00001% wt. up to about 5% wt., preferably from about 0.0001% wt. up to about 4% wt., more preferably from about 0.001% wt. up to about 3% wt., even more preferably from about 0.01% wt. up to about 2% wt., even more preferably from about 0.1% wt. up to about 1% wt., most preferably about 0.5% wt.

41. An agent according to claim 40, wherein the calcium-containing dentifrice and oral cavity care gel is a dental and oral care gel, in which the dendrimer is contained in an amount of 0.00001 -5 wt%, preferably 0.0001-4 % wt., more preferably 0.001 -3% wt., even more preferably 0.01-2% wt., even more preferably 0.1-1% wt., most preferably 0.5% wt.

42. An agent according to claim 31, wherein the calcium-containing dentifrice and oral cavity care product is a rinse for the care of the teeth and oral cavity.

43. The tool according to p. 42, where the calcium-containing means for caring for teeth and oral cavity is a rinse for caring for teeth and mouth, in which the dendrimer is contained in an amount from about 0.00001% wt. up to about 5% wt., preferably from about 0.0001% wt. up to about 4% wt., more preferably from about 0.001% wt. up to about 3% wt., even more preferably from about 0.01% wt. up to about 2% wt., even more preferably from about 0.1% wt. up to about 1% wt., most preferably about 0.5% wt.

44. An agent according to claim 43, wherein the calcium-containing dentifrice and oral cavity care product is a rinse for the care of teeth and oral cavity, in which the dendrimer is contained in an amount of 0.00001 -5 wt.%, Preferably 0.0001-4 % wt., more preferably 0.001 -3% wt., even more preferably 0.01-2% wt., even more preferably 0.1-1% wt., most preferably 0.5% wt.

45. An agent according to claim 31, wherein the calcium-containing dentifrice and oral cavity care product is a chewing gum for dental and oral care, foam, serum, aerosol, oral strips, ointment, irrigator liquid, tooth powder.