EA013370B1 - Formulation for prophylaxis of dental diseases - Google Patents

Abstract

Technical result of the invention is achieved by practical use of effective formulation containing accessible components based on biologically active agents of natural origin, which has a comprehensive effect on dental tissues and can be recommended for periodontium prophylaxis and treatment as well as caries and non-carious affections prophylaxis. The main purpose of this invention was to elaborate high-efficiency formulation for prophylaxis of dental diseases of teeth and soft tissues of oral cavity in which synergist medications could heighten effect of each other attaining high therapeutic effect and results mentioned above. Medicine for dental diseases prophylaxis contains orally acceptable active and inert components. As active components there are used about 0.3% to 2.2% by weight of lipid concentrate of sea kelps, 0.5 % to 5.0 % by weight of sea kelp salt, 0.5% to 4.0 % by weight of dry extract of liquorice, 0.01% to 0.25 % by weight of one or more ether oils to enhance organoleptic properties, and 0.1% to 3.5 % by weight of anticarious mineral adjunct.

Description

The invention relates to used in dentistry, therapeutic and prophylactic means for the care of the oral cavity, and specifically to the means for the prevention of dental diseases, which uses biologically active substances of natural origin.

Known level

Known composition for the prevention and treatment of diseases of the oral cavity, in particular gingivitis, in the form of gargling, toothpaste, which includes rosemary extract, and to increase the antibacterial effect - triclosan antiseptic (2006/0134025 A1, IPC A 61K 8/97 (2006.01) , 2006).

The treatment-and-prophylactic toothpaste is known, which contains an oily solution of plantain extract and an oily solution of needles extract, as well as Mexidol and calcium citrate (KI 2310436 C2, IPC A 61K 8/97 (2006.01), 2006). This composition is used for the prevention and treatment of caries, gingivitis, periodontitis, stomatitis, is aimed at preventing the formation of tartar or helps to reduce the mass of already formed tartar.

The closest analogue of the number of known compounds is the toothpaste, which is produced under the trademark "Ragoyopl"("Parodontaks") and includes bicarbonate soda and a mixture of natural ingredients, perfume, sodium fluoride. As natural ingredients, the composition includes a mixture of alcoholic extracts and oils of echinacea, myrrh, chamomile, ratania and sage (I8 2002/0031481 A1, IPC ⁷ A 61 K7 / 16, 2002).

This known composition contains bicarbonate soda soda as an abrasive in significant concentrations, more than 40 wt.%, Which creates a hypertonic environment, and this can cause loosening and recession of the gums. Thus, this toothpaste cannot be considered as a means for continuous, daily preventive care of teeth and gums. In addition, the known composition does not provide the necessary level of mineralization of hard dental tissues.

Summary of Invention

The technical result of the invention consists in the practical implementation using available components of a highly effective composition based on biologically active substances of natural origin, which implements the mechanism of complex effects on oral tissue and which can be recommended for the treatment and prevention of periodontal diseases, as well as for the prevention of caries and non-carious lesions . The immediate problem, which was solved by the invention, was to develop a highly effective composition for the prevention of dental diseases of the teeth and soft tissues of the oral cavity, in which the synergist drugs would enhance the effect of each other, providing a high therapeutic and preventive effect and achieving the above results.

The achievement of the technical result provides a composition for the prevention of dental diseases, which contains acceptable for oral use of active and inert components, where the active components used: lipid concentrate from sea brown algae 0.3-2.2 wt.%, Salt from sea brown algae 0.5-5.0 wt.%, Dry extract of licorice roots 0.5-4.0 wt.%, One or more essential oils to improve the organoleptic properties in an amount of 0.01-0.25 wt.%, As well as anti-caries mineral additive in the amount of 0.1 - 3.5% by weight.

In the best embodiment of the invention, the composition contains: lipid concentrate from sea brown algae - 0.5-1.8 wt.%, Salt from sea brown algae - 0.8-4.2 wt.%, Dry extract of licorice roots - 0, 8-3.6 wt.%, One or more essential oils - 0.03-0.22 wt.%.

Preferably, when to improve the organoleptic properties, one or more essential oils selected from the group including anise, thyme, lemon, mandarin, grapefruit, orange, bergamot, neroli, sage, tea tree, manuka, eucalyptus, fir, pine, juniper are used.

Literary sources indicate the value of biologically active substances contained in various types of marine brown algae. In particular, the prospects of obtaining lipid fractions from the laminaria of the northern and Far Eastern seas are shown (Study and use of preventive medical preparations based on natural biologically active substances. Edited by VG Bespalov and VB Nekrasova, St. Petersburg, Eskulap, 2000, p. 175-176).

Lipid fractions are obtained regardless of the species specificity of the algae as follows: extract the biologically active substances from the dried alga with ethyl alcohol or another volatile solvent, extract the solvent and separate the lipid concentrate and the aqueous extract. The most important biologically active components of the lipid concentrate: chlorophyll derivatives, carotenoids (beta-carotene), mannitol, polysaccharides, fatty acids, including essential ones (the bulk of the fatty acids are C18 and C20 omega-3 and omega-6), organically associated phosphorus and iodine, sulfoamino acids.

As you know, algae accumulate many elements very actively and concentrate many macro- and microelements. In the process of complex processing of marine brown algae emit inorganic salts. The biological properties of these compounds are determined by elements such as calcium.

- 1 013370 tions, iodine, potassium, magnesium, manganese, molybdenum, copper, cobalt, iron, germanium, selenium, zinc and others.

In general, natural biologically active substances isolated as a result of complex processing of marine brown algae, included in the composition for the prevention of dental diseases, lead to increased metabolic processes, improved trophism and blood circulation in periodontal tissues, which reduces the process of atrophy of the alveolar process, contribute to an increase in non-specific resistance .

The use of extracts of licorice root as a drug has been around for millennia. Drug capabilities are determined by the chemical composition: the roots of licorice contain 623% triterpenic saponin glycyrrhite, mixed potassium-calcium-magnesium salt of glycyrrhizinic acid, and glycyrrhizinic acid, glybric, 18-glycyrrhetic, 18,19-dihydroglycyrrhicic acid, 11,19-dihydroglycyrrhicic acid; up to 4% of flavonoids: likvritin, izoliquiritin, lycurazide, neolikviritin, glabrozid, uralozide, likvritozid, glabrone, quercetin, kaempferol, apigenin, onion mono - and disaccharides (up to 20%); starch (up to 34%); pectins (4-6%); resin (4%); phenol carboxylic acids and their derivatives (3-6%): salicylic acid acetate, salicylic acid, ferulic acid; coumarins: geraniarin, liquyumarin; tannins (up to 14%); alkaloids; essential oil; organic acids: tartaric, citric, malic, fumaric; steroids - beta-sitosterol, estriol; macronutrients: potassium, calcium, magnesium, iron; trace elements: manganese, copper, zinc, barium, vanadium, selenium, nickel, strontium. 80 triterpenoids, over 300 individual phenolic compounds, several dozen polysaccharides, amino acids and many other substances have been isolated and described from licorice (Herbal medicine with the basics of clinical pharmacology. Edited by VG Kukes. M. Medicine, 1999, p. 66-67).

Glabridine and glabrene, likohalkon, licoricidin, and likoisoflavone B flavonoids showed antimicrobial activity against Neysoborun in a study of η νίίτο.

These flavonoids are also active in relation to clarithromycin and amoxicillin of resistant strains of Nexobus ruterop (Ricksh T., Magito A., Which K., e! A1. An! 1 — Not Coach! Er ρνίοπ Πανοηοίάδ 1gosh ksopse ex! Gas! 8c1. 2002, Hades 9; 71 (12): 1449-63).

Several flavonoid extracted from licorice (glabridin, likohalkon) demonstrated antimicrobial activity against strains metsitillinrezistentnyh 8! Arku1osossib aureus with minimal inhibitory concentrations 3,13-12,5 mg / ml, flavonoids glabren, likoizoflavon, likoizoflavonol also shown ativnost against these strains concentration of 1.56-25.0 µg / ml. (Rika1 T., Magito A., Kak K., e! A1. An! 1Sh1sgo1a1 as! M! At the cops ίηνοηοίάδ adats! Those! K1ssSh-818! Ap! 8! Arcossossiz aegeib. P1! , Wasps!; 73 (6): 536-9).

In the study of the solubility of enamel powder ίη νίίτο in acidic acetate buffer and saliva, to which glucose was added, it was shown that adding 0.1 M ammonium glycyrrhizate (from licorice root extract) reduces solubility by 30%, and during incubation for 18 h by 60% compared with solutions without ammonium glycyrrhizate. This effect can be explained by the ability of glycyrrhizic acid to inhibit glycolysis and exhibit buffering properties, that is, glycyrrhizic acid may presumably have potential cariesstatic properties. (\ W.M. Ebdag Kebisbop ίη Epashe1 88ο1υ! Ίοη Lacus. | Iopse App Susuggi / yis Aab. REep! Kez 57 (1): 59-64 1st Italy 1978).

In addition to numerous medical aspects of the use of drugs from licorice roots, it is very attractive to use this extract in oral hygiene products for a long time by man in the food industry to make halva, licorice candies.

It is necessary to note the role of microelements, which are present both in the extract of licorice root and in salt from sea brown algae. The physiological effect and participation of microelements in biochemical metabolic reactions in dental tissues to a certain extent is revealed on the basis of data on the general principles of the processes of metabolism and mineralization of hard tissues — teeth and bone. The process of mineralization occurs under the influence of biological activators, one of them is phosphatase, which are many in the buds of teeth. It is possible that the action of trace elements is manifested through the activation of phosphatases. It can be assumed that certain trace elements can take part in the formation of the nucleolus of mineralization due to attachment to collagen and the formation of metalloprotein active complexes. In mature teeth, trace elements can have a direct effect or by combining with a nonspecific protein present in the dental lymph, as a result of which biologically active substances are formed (Kodola N. A. Trace elements in the prevention of dental caries. Kiev, Zdorovya, 1979, p. 22- 23).

Due to the fact that the lipid concentrate of sea brown algae has a specific aroma that causes some consumers to notice, it has been proposed to add one or more essential oils to the toothpastes that can mask this unpleasant odor. Essential oils were chosen from the following group: anise, thyme, lemon, mandarin, grapefruit, bergamot, neroli, sage, tea tree, manuka, eucalyptus, fir, pine, juniper. Licorice root extract also has a beneficial effect on the aroma of toothpaste. Essential oils themselves and in combination with licorice root extract have a broad antimicrobial spectrum of action.

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The concept of remineralization is part of the ideology of the developed composition. The remineralizing system is a combination of ingredients that allow the enamel of healthy teeth and initial foci of carious lesion to be filled with minerals.

Optimal when carrying out the invention is the content of the anti-caries mineral additive of 0.2-3.3 wt.%.

It is preferable to use calcium glycerophosphate and inorganic or organic magnesium salt as an anti-caries mineral additive.

As an inorganic or organic magnesium salt, substances selected from the group consisting of magnesium chloride, magnesium sulfate, magnesium nitrate, magnesium citrate, magnesium lactate, magnesium glycerophosphate, magnesium acetate, magnesium ascorbyl phosphate can be used.

The need for supplements due to the need of teeth in these elements for caries, and even more so for non-carious lesions of the teeth. Calcium and phosphorus are the main building blocks of tooth enamel and participate in metabolic processes throughout a person’s life.

Non-carious teeth lesions are most often associated with disorders of calcium metabolism and occur with adverse effects of an endogenous nature (dysfunction of the thyroid gland, pancreas, gonads, diseases of the gastrointestinal tract, etc.), as well as under the influence of external adverse effects (ionizing radiation, daily long-term work of more than 6 hours with a computer, the influence of production factors: acid vapors, metallic dust and their combinations, a number of negative environmental influences) causing noticeable loss of mineral components in the tissues of the teeth, and then to damage in the form of caries, erosion, wedge-shaped defects, abrasion of teeth.

Topical application of treatment-and-prophylactic compositions containing phosphoric-calcium additives, allows not only to prevent, but also to a certain extent, to compensate for losses in the presence of the disease.

Calcium glycerophosphate is a source of active intake of phosphorus and calcium in the teeth and periodontal tissues, which accelerates the mineralization processes and increases the anti-caries effect of the composition, enhances the anabolic processes in the tissues.

Magnesium (from the composition of inorganic or organic salts) is a structural component of the teeth and introduced into the complex as a trace element, which is a cofactor for phosphatases that ensure the incorporation of phosphates into the hard tissues of the teeth. Under the influence of phosphatases, glycerophosphate is hydrolyzed and its bioavailability increases accordingly.

Since in the absence of dense plaque the risk of demineralization of the teeth is significantly reduced, the composition may not include fluorides. The presence of fluoride in the composition to care for the oral cavity is important in a situation where a soft plaque during the decomposition of easily fermentable carbohydrates produces organic acids. However, even under these conditions, after the completion of the ripening process of tooth enamel (in persons older than 20 years), local fluoride action is practically not felt, which results in a decrease in their effectiveness for the prevention of caries.

However, the proposed composition assumes that the anti-caries mineral additive may additionally contain one or more substances selected from the group including sodium monofluorophosphate, potassium monofluorophosphate, calcium monofluorophosphate, magnesium monofluorophosphate, in an amount of 0.6-1.8 wt.%.

The composition is preferably made in the form of toothpaste.

In this case, from among the inert components, it contains, in wt.%:

abrasive component - 10-38, moisturizing component -11-50, gel-forming component - 0.5-7, at least one surfactant - 0.5-3, at least one flavoring filler - 0.5-2 , at least one preservative - 0.01-0.5.

In the preparation of toothpaste, one or more substances selected from the group including dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, calcium carbonate, silicon dioxide, aluminum oxide, aluminum hydroxide, polymethacrylate can be used as an abrasive component.

As a moisturizing component of toothpaste can be used one or more substances selected from the group including sorbitol, glycerin, polyethylene glycol, propylene glycol.

As a gel-forming component of toothpaste, one or several substances selected from the group including hydroxyethylcellulose, xanthan gum, guar gum, carboxymethylcellulose, potassium alginate, sodium alginate, silicon dioxide thickener can be used.

From the number of surfactants in the preparation of the composition for the prevention of dental diseases in the form of toothpaste can be used one or more substances selected from the group including sodium lauryl sulfate, alkylamidobetaine, polysorbate-20, sodium

- 3 013370 lauryl sarcosinate.

One or more substances selected from the group that includes essential oils - peppermint, spearmint, cloves, wintergreen, ginger, as well as menthol, carvon, anethole, eucalyptol, methyl salicylate, sweeteners - sodium saccharinate, potassium can be used as a flavoring filler. aspartame, potassium acesulfame, stevioside, xylitol, potassium or sodium glycyrrhizate.

As a preservative, one or several substances selected from the group including methylparaben, propylparaben or their sodium salts, phenoxyethanol, benzoic acid, sodium benzoate, potassium sorbate can be used.

The implementation of the invention

The possibility of implementing the composition for the prevention of dental diseases is illustrated by examples of toothpastes, the qualitative and quantitative composition of which is presented in Table. one.

Toothpastes are prepared as follows.

Weigh the required amount of glycerin, to which gum xanthan is added. Stir until a homogeneous mass.

Weigh the required amount of water in the dispenser and load water into the mixer, to which stevioside, sodium benzoate, sorbitol, salt from sea brown algae, sodium monofluorophosphate (in the case of examples 4, 5), magnesium chloride (in the case of examples 1, 2, 3) are added. . Stir until a clear solution is formed.

In the resulting solution load suspension xanthan gum in glycerin and mix until a homogeneous mass. The composition is vacuum and stirred for 10 minutes until complete removal of air from the mixture.

Table 1

Example 1 Example 2 Example 3 Example 4 Example 5 concentration, May. % Glycerol 22 sixteen ten eight five Sorbitol - ten sixteen 22 thirty Dicalcium phosphate dihydrate eleven 23 38 - - Calcium carbonate five ten - 35 38 Silicon dioxide thickening 6 four 3.5 2.8 - Gum xanthan 0.9 1.1 1.2 1.2 0.8 Sea kelp salt one 2 2.5 3.2 four Lipid concentrate sea kelp 0.6 0.8 1.8 one 0.7 Dry Licorice Extract 0.8 1.2 2.5 2.8 3.4 Sodium monofluorophosphate - - - 1.1 0.8 Calcium glycerophosphate 1.2 one 0.8 0.6 0.1 Magnesium glycerophosphate - - - 0.1 0.05 Magnesium chloride 0.1 0.2 0.5 - - Sodium lauryl sulfate 1.4 1.2 0.8 - - Alkylamidobetaine - 1.0 1.5 1,3 0.6 Sodium benzoate 0.4 0.3 0.2 0.12 0.08 Lemon essential oil 0.04 0.12 0.08 0.05 - Thyme Essential Oil - - 0.08 0.12 0.2 Stevioside 0.1 0.15 0.2 0.3 0.2 Odorant 0.6 0.8 0.9 1.2 1.5 Water Up to 100% Up to 100% Up to 100% Up to 100% Up to 100%

After that, calcium glycerophosphate or magnesium glycerophosphate (in the case of examples 4, 5) is added, stirred for 15-20 minutes.

Then add thickening silica (in case of examples 1, 2, 3, 4), calcium carbonate (in examples 1, 2, 4, 5), dicalcium phosphate dihydrate (in examples 1, 2, 3), vacuum and mix for 40-50 min.

Next, the toothpaste is homogenized using a homogenizer pump for 10-20 minutes. A fragrance, an essential oil or a mixture of essential oils (examples 3, 4), as well as a seaweed lipid concentrate are loaded into the mixer. Stir until a homogeneous mass for 20-30 minutes.

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Download dry extract of licorice roots, sodium lauryl sulfate (in examples 1, 2, 3), alkylamidobetaine (in the case of examples 2, 3, 4, 5) and mix until a homogeneous mass for 20-30 minutes. Cooked toothpaste is packaged in tubes of polymeric material.

Efficiency mark

The effectiveness of the toothpaste prepared in accordance with the invention was tested on a group of volunteers in order to evaluate the anti-inflammatory action. Used the composition according to example 3 of table. 1. As a comparison, Parodontax toothpaste was used, prepared in accordance with the above-mentioned analogue.

The clinical study involved 2 groups of 15 and 16 people. Persons aged 15 to 45 years were selected with a diagnosis of chronic catarrhal gingivitis or chronic mild periodontitis. The duration of the experiment was 14 days. Anti-inflammatory effect was evaluated using the PMA index definition (S. Ragta, 1964). The evaluation of the index values was determined before the beginning of the study and at its end, i.e. in 14 days.

These clinical indicators are presented in Table. 2

table 2

PMA,% Toothpaste "Parodontaks" Toothpaste in example 3 Prior to the study 16.35 ± 2.22 20.61 ± 2.60 After 14 days of use 5.18 ± 0.66 6.28 ± 1.15

Thus, in the case of using toothpaste prepared in accordance with example 3 of table. 1, a reduction of 69.5% is observed, and in the case of Parodontax toothpaste - 68.3%. That is, the index of gingivitis in the case of using the composition prepared in accordance with the invention, decreases more pronounced.

Consequently, a highly effective and affordable therapeutic and prophylactic composition in the form of toothpaste, which implements the mechanism of complex effects on oral tissue, has been created.

This composition in the form of toothpaste can be recommended for the treatment and prevention of periodontal diseases, as well as for the prevention of caries and non-carious lesions. Possible embodiments of the invention in the form of a gel or a liquid means (rinse, elixir), which also extends to the legal protection provided for all cases of the implementation of the composition for the prevention of dental diseases.

Claims (17)

CLAIM 1. Agent for the prevention of dental diseases, containing active and inert components acceptable for oral use, characterized in that it has the following composition: active ingredients - lipid concentrate from marine brown algae 0.3-2.2 wt.%, salt from marine brown algae 0.5-5.0 wt.%, dry extract of licorice roots 0.5-4.0 wt.% , one or more essential oils to improve the organoleptic properties in the amount of 0.01-0.25 wt.%, as well as anti-caries mineral additive in the amount of 0.1-3.5 wt.%, inert components - up to 100 wt.%. 2. The tool according to claim 1, characterized in that the content of the concentrate of lipids from marine brown algae is 0.5-1.8 wt.%. 3. The tool according to claim 1, characterized in that the salt content of marine brown algae is 0.8-4.2 wt.%. 4. The tool according to claim 1, characterized in that the content of the dry extract of licorice roots is 0.8-3.6 wt.%. 5. The tool according to claim 1, characterized in that the content of one or more essential oils is 0.03-0.22 wt.%. 6. The tool according to claim 1, characterized in that the essential oils are selected from the group comprising anise oil, thyme, lemon, mandarin, grapefruit, orange, bergamot, neroli, sage, tea tree, manuka, eucalyptus, fir, pine, juniper . 7. The tool according to claim 1, characterized in that the content of the anti-caries mineral additive is 0.2-3.3 wt.%. 8. The tool according to claim 1, characterized in that as an anti-caries mineral additive it contains calcium glycerophosphate and inorganic or organic magnesium salt. 9. Means under item 8, characterized in that as an inorganic or organic magnesium salt, it contains salts selected from the group including magnesium chloride, magnesium sulfate, magnesium nitrate, magnesium citrate, magnesium lactate, magnesium glycerophosphate, magnesium acetate, magnesium ascorbyl phosphate. 10. The tool of claim 8, wherein the anti-caries mineral additive additionally contains one or more substances selected from the group including sodium monofluorophosphate, potassium monofluorophosphate, calcium monofluorophosphate, magnesium monofluorophosphate in the amount of 0.6-1.8 wt.%. 11. The tool according to claim 1, characterized in that if it is a toothpaste, as an inert component, it contains, wt%: abrasive component 10-38, moisturizing com - 5 013370 ponent 11-50, gel-forming component 0.5-7, at least one surfactant 0.5-3, at least one flavor filler 0.5-2, at least one preservative 0.01 -0.5. 12. The tool according to claim 11, characterized in that one or more substances selected from the group including dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, calcium carbonate, silicon dioxide, aluminum oxide, aluminum hydroxide, polymethacrylate are used as an abrasive component. 13. The tool according to claim 11, characterized in that as a moisturizing component it contains one or more substances selected from the group comprising sorbitol, glycerin, polyethylene glycol, propylene glycol. 14. The tool according to claim 11, characterized in that as a gel-forming component it contains one or more substances selected from the group including hydroxyethyl cellulose, xanthan gum, guar gum, carboxymethyl cellulose, potassium alginate, sodium alginate, silicon dioxide thickening. 15. The tool according to claim 11, characterized in that as a surfactant it contains one or more substances selected from the group including sodium lauryl sulfate, alkylamidobetaine, polysorbate-20, sodium lauryl sarcosinate. 16. The tool according to claim 11, characterized in that as a flavoring filler it contains one or more substances selected from the group that includes essential oils - peppermint, curly mint, clove, wintergreen, ginger, as well as menthol, carvone, anethole , eucalyptol, methyl salicylate, sweeteners - sodium saccharinate, potassium aspartame, potassium acesulfame, stevioside, xylitol, potassium or sodium glycyrrhizate. 17. The tool according to claim 11, characterized in that as a preservative it contains one or more substances selected from the group including methylparaben, propylparaben or their sodium salts, phenoxyethanol, benzoic acid, sodium benzoate, potassium sorbate.