RU2535051C1 - Tooth paste - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to oral hygiene products. The presented tooth paste comprises lysine, papaine, dextranase, alpha amylase, glucoamynase, superoxide dismutase, glucose oxydase, lactoperoxidase or peroxidise, invertase, cytochrome-c-oxidase, as well as sphagnum or cedar extract, dipotassium glycyrizinate, potassium thiocyanate, sodium-calcium salt of poly(methyl vinyl ether-co-maleic acid), betaine, DL-pyrrolidone carboxylate N-cocoyl ethyl arginate and sodium fluoride, a polymer thickener, an emulsifier, a flavouring agent, sorbitol 70%, demineralised water.

EFFECT: tooth paste composition provides the effective oral cleansing and tooth deposit removal with using no abrasives, reducing oral angiostaxis and inflammations, and also promotes remineralising dental enamel.

4 cl, 11 tbl, 3 ex

Description

The present invention relates to dentistry, namely, toothpaste for remineralizing enamel and reducing tooth sensitivity, cleaning the oral cavity, treating and preventing tooth decay, periodontal disease and the oral mucosa, containing the following components: lysine, enzymes: papain, dextranase, alpha- amylase, glucoamylase, superoxide dismutase, glucose oxidase, lactoperoxidase or peroxidase, invertase, cytochrome C oxidase, sphagnum or thuja extract, dipotassium glycyrrhizinate, potassium thiocyanate, sodium calcium salt Limeray polimetilvinilovogo alcohol and maleic acid, betaine, DL-pyrrolidone carboxylate N-cocoyl etilarginata and sodium fluoride, a polymer thickener, emulsifier, flavor, sorbitol 70% demineralised water.

The invention allows to reduce without the use of abrasive materials such as calcium carbonate, calcium pyrophosphate, dicalcium phosphate, silicon dioxide, aluminum hydroxide, the formation of plaque on the surface of the teeth by 62.06% due to the enzymatic destruction of plaque, remineralization of tooth enamel and the destruction of pathogenic microflora , reduce inflammation in the oral cavity by 85.11%. Toothpaste does not contain highly abrasive components and has good organoleptic properties: it is white in color, with a pleasant smell and good taste.

There are various medicinal and preventive toothpastes used for the prevention of inflammatory periodontal diseases, containing anti-caries and anti-inflammatory components that are not enzymes, for example, sodium fluoride, extracts of medicinal plants and vitamins (Medical and preventive toothpaste "Silca Herb plus" (Germany), Tea tree oil Toothpaste "Natural whitening toothpaste with tea tree oil" (USA). However, this paste has a low cleaning ability, because it does not contain components that dissolve directionally slaughter.

Known medical and preventive toothpaste Control RX 5000 ppm NaF containing poloxamer 407 and dimethicone for plaque removal and prevention of periodontal disease (http://rudocs.exdat.com/docs/index-566873.html?page=9#794395) .

Known desensitizing paste Colgate® Sensitive Pro-Relief ™ containing arginine and calcium carbonate to reduce tooth sensitivity (http://www.colgateprofessional.ru/products/5938a27a02315210b27a0231521028016e0aRCRD/specifics).

Known mouthwash elmex® SENSITIVE PLUS to reduce tooth sensitivity and anticaries protection, containing aminofluoride for sealing dentinal tubules and PVP / Dimethylaminoethyl methacrylate polycarbamoyl polyglycol, forming a protective film on the surface of the tooth

(http://www.colgateprofessional.ru/products/65f8a27a02315210b27a0231521028016e0aRCRD/details).

Known toothpaste Colgate® Total for daily use, which has antibacterial and anti-inflammatory effects for 12 hours, containing sodium fluoride and a complex of Triclogard based on triclosan and a copolymer of polymethyl vinyl alcohol with maleic anhydride (PVM / MA copolymer)

(http://www.colgateprofessional.ru/products/5fe8a27a02315210b27a0231521028016e0aRCRD/details).

Known toothpaste with an enzyme-containing composition, where the enzyme is selected from the group of proteinases including papain (Rembrandt Whitening Toothpaste (USA), as well as a paste containing betaine, lysozyme, glucose oxidase, lactoperoxidase and lactoferrin (Biotene toothpaste) "(Finland), which is used to treat xerostomia. The described toothpaste does not contain D, L-pyrrolidone carboxylate n-cocoyl ethylarginate, which has the ability to normalize the microflora of the oral cavity, and therefore cannot be used to control pathogenic oh microflora.

From RU 2355420, publ. 05/20/2009 (examples, claims), a toothpaste is known, including: an abrasive component - silicon dioxide, lactulose - 2.0-6.0 wt.%, A combination of enzymes: papain - 0.2-1.0 wt.% and lysozyme 0.01-0.4 wt.%. Toothpaste also contains: sodium carboxymethyl cellulose - 0.5-0.7 wt.%, Preservatives (sodium methylparaben and sodium propylparaben) in a total amount of 0.2-0.8 wt.%, Sodium lauryl sulfate and sodium lauroyl sarcosinate in total - 0.6-3.0 wt.%, Flavoring - 0.05-2.0 wt.% And demineralized water. In RU 2355420, publ. 05/20/2009 (examples, claims), it is also indicated that the introduction of lactulose in the composition of the toothpaste helps to restore the natural microflora of the oral cavity.

From US 4150113, publ. 04/17/1979 (the entire document, in particular, the description column 5, examples, claims), dentifrices are known, including toothpastes, mouth rinses, chewing tablets and gums, the main active ingredient of which is glucose oxidase. It is indicated that in addition to glucose oxidase, it is advisable to include carbohydrase, for example, alpha-amylase, glucoamylase (amyloglucosidase), dextranase, and invertase.

From US 4578265, publ. 03/25/1986 (examples, claims), a dentifrice with antibacterial properties is known, including glucose oxidase, lactoperoxidase and potassium or ammonium thiocyanate.

However, these agents do not contain proteases, in particular papain.

From RU 2333768, publ. September 20, 2008 (see the Enzymes section), it is also known that it is advisable to include carbonic anhydrases such as glucoamylase, alpha-amylase, dextranase, and proteases, such as papain, in the compositions for caring for the oral cavity. Moreover, this combination of enzymes can be supplemented with lysozyme. However, these compositions do not contain D, L-pyrrolidone carboxylate N-cocoyl ethylarginate.

Closest to the claimed invention is RU 2407512, from which a non-abrasive toothpaste is known containing enzymes papain, dextranase, alpha-amylase, potassium or ammonium thiocyanate, invertase or glucoamylase, glucose oxidase, lactoperoxidase, lysozyme or lactoferulactin and. RU 2407512 provides data on the cleaning, anti-inflammatory, hemostatic effectiveness of toothpaste, as well as on the restoration of the natural microflora of the oral cavity when it is used. The claimed paste differs from that known from RU 2407512 in that it additionally contains lysine, dipotassium glycyrrhizinate, sphagnum or thuja extract, D, L-pyrrolidone carboxylate N-cocoyl ethylarginate, sodium fluoride, betaine, calcium-sodium salt of a polymethylvinyl alcohol copolymer and maleic acid, enzymes: superoxide dismutase, cytochrome c-oxidase, and also contains enzymes: invertase and glucoamylase.

Toothpastes containing lysine, enzymes: papain, dextranase, alpha-amylase, glucoamylase, superoxide dismutase, glucose oxidase, lactoperoxidase or peroxidase, invertase, cytochrome c-oxidase, sphagnum or thuia extract, dipotassium glycyrrhizin polimerithiolate cytolimerin trisolithryolate alcohol and maleic acid, betaine, d, l-pyrrolidone carboxylate n-cocoyl ethylarginate and sodium fluoride to remineralize enamel and reduce tooth sensitivity, cleanse the mouth, treat and prevent tooth decay, disease s periodontal and oral mucosa are not described.

Thus, an object of the present invention is to provide a toothpaste containing lysine, enzymes: papain, dextranase, alpha-amylase, glucoamylase, superoxide dismutase, glucose oxidase, lactoperoxidase or peroxidase, invertase, cytochrome c-oxidase, sphagnum extract or dipotassium glycyrrhizinate, potassium thiocyanate, sodium-calcium salt of a copolymer of polymethyl vinyl alcohol and maleic acid, betaine, d, l-pyrrolidone carboxylate n-cocoyl ethyl arginate and sodium fluoride and not containing highly abrasive components s which may be used for remineralization of the enamel and reduce tooth sensitivity, cleansing the oral cavity, the treatment and prevention of caries, periodontal disease and oral mucosa.

According to the present invention, a toothpaste is provided, characterized in that it contains: 0.01-5.0 wt.% Lysine, 0.01-5.0 wt.% Papain, 0.01-5.0 wt.% Dextranase, 0 , 01-5.0 wt.% Alpha-amylase, 0.01-5.0 wt.% Glucoamylase, 0.01-5.0 wt.% Superoxide dismutase, 0.01-5.0 wt.% Glucose oxidase, 0 , 01-5.0 wt.% Lactoperoxidase or peroxidase, 0.01-5.0 wt.% Invertase, 0.01-5.0 wt.% Cytochrome c-oxidase, 0.01-5.0 wt.% sphagnum or thuja extract, 0.01-5.0 wt.% dipotassium glycyrrhizinate, 0.01-0.5 wt.% potassium thiocyanate, 0.01-5.0 wt.% betaine, 0.01-5.0 wt.% D, L-pyrrolidone carboxylate N-cocoyl ethylarginate, 0.01-5.00 wt.% n calcium atrii salt of a copolymer of polymethyl vinyl alcohol and maleic acid, 0.05-0.26 wt.% sodium fluoride, as well as acceptable carriers and excipients, including a polymer thickener, emulsifier, flavor, 70% sorbitol, demineralized water.

As a preferred embodiment of the claimed invention, the toothpaste indicated above, in the following ratio of components, wt.%:

Lysine 0.01-5.00 Papain 0.01-5.00 Dextranase 0.01-5.00 Alpha amylase 0.01-5.00 Glucoamylase 0.01-5.00 Superoxide dismutase 0.01-5.00 Glucose oxidase 0.01-5.00 Lactoperoxidase 0.01-5.00 Invertase 0.01-5.00 Cytochrome c oxidase 0.01-5.00 Betaine 0.01-5.00 Sphagnum extract 0.01-5.00 Dipotassium glycyrrhizinate 0.01-5.00 Potassium thiocyanate 0.01-0.50 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01-5.00 Sodium Fluoride 0.05-0.26 Sodium-calcium salt of the copolymer polymethyl vinyl alcohol and maleic acid 0.01-5.00 Sodium carboxymethyl cellulose 0.50-0.70 Emulsifier 0.01-5.00 Flavoring 0.01-1.00 Sorbitol 70% 5.00-10.00 Demineralized water Rest

As another preferred embodiment of the claimed invention, the toothpaste indicated above, in the following ratio of components, wt.%:

Hydroxyapatite 0.01-5.00 Lysine 0.01-5.00 Papain 0.01-5.00 Dextranase 0.01-5.00 Alpha amylase 0.01-5.00 Glucoamylase 0.01-5.00 Superoxide dismutase 0.01-5.00 Glucose oxidase 0.01-5.00 Peroxidase 0.01-5.00 Invertase 0.01-5.00 Cytochrome c oxidase 0.01-5.00 Betaine 0.01-5.00 Sphagnum extract 0.01-5.00 Dipotassium glycyrrhizinate 0.01-5.00 Potassium thiocyanate 0.01-0.50 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01-5.00 Sodium Fluoride 0.05-0.26 Sodium-calcium salt of the copolymer polymethyl vinyl alcohol and maleic acid 0.01-5.00 Carrageenan 0.50-0.70 Emulsifier 0.01-5.00 Flavoring 0.01-1.00 Sorbitol 70% 5.00-10.00 Demineralized water Rest

As another preferred embodiment of the claimed invention, the toothpaste indicated above, in the following ratio of components, wt.%:

Hydroxysomes ™ 0.01-5.00 Lysine 0.01-5.00 Papain 0.01-5.00 Dextranase 0.01-5.00 Alpha amylase 0.01-5.00 Glucoamylase 0.01-5.00 Superoxide dismutase 0.01-5.00 Glucose oxidase 0.01-5.00 Peroxidase 0.01-5.00 Invertase 0.01-5.00 Cytochrome c oxidase 0.01-5.00 Betaine 0.01-5.00 Thuja extract 0.01-5.00 Dipotassium glycyrrhizinate 0.01-5.00 Potassium thiocyanate 0.01-0.50 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01-5.00 Sodium Fluoride 0.05-0.26 Sodium-calcium salt of the copolymer polymethyl vinyl alcohol and maleic acid 0.01-5.00 Xanthan gum 0.50-0.70 Emulsifier 0.01-5.00 Flavoring 0.01-1.00 Sorbitol 70% 5.00-10.00 Demineralized water Rest

The active ingredients of the claimed toothpaste are: hydroxyapatite, Hydroxysomes ™, lysine, enzymes: papain, dextranase, alpha-amylase, glucoamylase, superoxide dismutase, glucose oxidase, lactoperoxidase or peroxidase, invertase, cytosulfate oxidase, cytochrome oxidase, oxidase oxidase, cytosulfate oxidase, cytosulfate oxidase, cytosulfate oxidase, cytosulfate oxidase, cytosulfate oxidase, cytosulfate oxidase, calcium oxide sodium-calcium salt of a copolymer of polymethylvinyl alcohol and maleic acid, betaine, d, l-pyrrolidone carboxylate n-cocoyl ethylarginate and sodium fluoride. Hydroxysomes ™, the main component of which are hydroxyapatite molecules, contribute to the mineralization of hard tooth tissues and the immobilization of enzymes. Lysine neutralizes acids and is a substrate for the synthesis of collagen fibers of periodontal tissues. Papain is capable of breaking peptide bonds from sulfur-containing amino acid residues. Alpha-amylase hydrolyzes starch and amylopectin to dextrans and dextrins. Dextranase hydrolyzes dextrans and dextrins to oligosaccharides. Glucoamylase hydrolyzes oligosaccharides to monosaccharides. Invertase hydrolyzes sucrose into fructose and glucose. Glucose oxidase oxidizes glucose with the formation of hydrogen peroxide, together with lactoperoxidase or peroxidase, potassium or ammonium thiocyanate forms the so-called lactoperoxidase (peroxidase) system, the principle of which is as follows: hydrogen peroxide oxidase oroxidonate oxidizes in the presence of glucose oxidase or hypothiocyanates that can damage the cell wall of pathogenic microorganisms. Superoxide dismutase restores the superoxidones produced during lipid peroxidation during inflammation to oxygen and hydrogen peroxide. Oxygen is further utilized by cytochrome c-oxidase for oxidative phosphorylation to form water, and hydrogen peroxide is included in the cycle of the lactoperoxidase (peroxidase) system. D, L-pyrrolidone carboxylate N-cocoyl ethylarginate and sodium fluoride during the preparation of the composition, interacting with each other during the exchange reaction, form D, L-pyrrolidone carboxylate sodium and N-cocoyl ethyl arginate fluoride. D, L-pyrrolidone carboxylate sodium has a moisturizing effect on the oral mucosa, preventing xerostomia. During toothbrushing, N-cocoyl ethylarginate fluoride forms a stable layer on the enamel surface that inhibits the development of pathogenic microflora and simultaneously deposits fluoride ions, contributing to the slow remineralization of tooth enamel. Sodium-calcium salt of a copolymer of polymethylvinyl alcohol and maleic acid, having high adhesiveness with respect to tooth tissues, is firmly fixed on tooth enamel and creates a calcium depot. Betaine, having the property of bipolarity, contributes to the retention of water by the connective tissue of the gums and the fixation of calcium ions on the surface of the tooth. Dipotassium glycyrrhizinate has anti-inflammatory, antiviral and antimicrobial effects, and in combination with sphagnum extract ensures the elimination of inflammatory phenomena in the oral cavity.

Thus, the integrated use of the above active components leads to the following result: plaque modification with the formation of easily removable water-soluble compounds, the creation of depots on the surface of the teeth: calcium, fluoride and a soft antiseptic, with the aim of remineralization of enamel and dentin, obstruction of the dentinal tubules, antimicrobial and anticaries protection against the effects of pathogenic microorganisms; prevention of inflammatory periodontal diseases. The following substances are used to prepare toothpaste: “Hydroxyapatite with a particle size of 80 nm to 5 μm”, “Potassium thiocyanate 97%”, “Lysine hydrate 97%”, “Dicalia glycyrrhizinate 97%", "Betaine anhydrous 97%", "Papain "," Hydroxysomes ™ "," Peroxidase "," Superoxide Dismutase "," Glucose Oxidase "," Lactoperoxidase "," Dextranase "," Invertase "," Glucoamylase "," Alpha-Amylase "," Cytochrome C (cytochrome c-oxidase) "," Sphagnum extract "," D, L-pyrrolidone carboxylate N-cocoyl ethylarginate (CAE) "," Sodium fluoride "," Sodium-calcium salt of polymethylvinyl copolymer Peart and maleic acid (Gantrez ™ MS-955). " Papain is obtained from papaya fruits by extraction from crushed raw materials, followed by purification and freeze drying. Freeze-dried powder "Papain" is used in medicine together with lysozyme for the treatment of intervertebral hernia, in the form of powders and lotions in dentistry for gingivitis and periodontitis, and other inflammatory conditions of the oral cavity. Sphagnum and thuja extracts are used to treat various inflammatory diseases. D, L-pyrrolidone carboxylate N-cocoyl ethylarginate is used as a preservative. Sodium-calcium salt of a copolymer of polymethylvinyl alcohol and maleic acid (Gantrez ™ MS-955. Used as a means for fixing dentures. Dicalium glycyrrhizinate isolated from licorice extract is used as an antimicrobial agent. Peroxidase obtained from whey, horseradish root, radish , is used as a diagnostic tool in enzyme immunoassay. Hydroxysomes ™ are used in the cosmetics industry as a carrier of active ingredients. Hydroxyapatite is used in one hundred atopicology as part of the Collapol preparation for osteoplasty. Betaine is used as a moisturizing and conditioning additive in cosmetics. Lysine is a part of various dietary supplements as a source of irreplaceable acid. Dextranase is available in tablets for caries prevention. Alpha amylase, invertase, glucoamylase are used in food industry.

The toothpaste of the present invention is usually made by conventional methods using solid or liquid acceptable carriers or excipients selected from emulsifiers, dispersants, preservatives, flavorings, pH adjusters, polymer carriers and other excipients that are suitable for preparing compositions for topical application.

Additional advantages of this composition are the ability to remineralize tooth enamel and restore the natural microflora of the oral cavity.

The proposed toothpaste reduces plaque formation by 75% and is completely harmless and safe for prolonged use.

The significant differences of the proposed toothpaste are as follows.

The claimed cosmetic composition has stability with respect to the activity of the enzymes included in its composition during prolonged storage, which is achieved by immobilizing the enzymes on polymer carriers contained in the specified composition. As these polymeric carriers, any polymeric thickeners capable of binding to enzymes to form enzyme-carrier complexes can be used. Examples of such polymer thickeners are sodium carboxymethyl cellulose, carrageenan, xanthan gum, poloxamers, polyquaternium, hydroxypopyltrimmonium chloride.

The activity of the claimed composition is due to the activity of its active ingredients. It was found that a toothpaste containing: 0.01-5.0 wt.% Lysine, 0.01-5.0 wt.% Papain, 0.01-5.0 wt.% Dextranase, 0.01-5, 0 wt.% Alpha-amylase, 0.01-5.0 wt.% Glucoamylase, 0.01-5.0 wt.% Superoxide dismutase, 0.01-5.0 wt.% Glucose oxidase, 0.01-5, 0 wt.% Lactoperoxidase or peroxidase, 0.01-5.0 wt.% Invertase, 0.01-5.0 wt.% Cytochrome c-oxidase, 0.01-5.0 wt.% Sphagnum or thuja extract, 0.01-5.0 wt.% Dipotassium glycyrrhizinate, 0.01-0.5 wt.% Potassium thiocyanate, 0.01-5.0 wt.% Betaine, 0.01-5.0 wt.% D, L-pyrrolidone carboxylate N-cocoyl ethyl arginate, 0.01-5.00 wt.% Sodium-calcium salt of polymethyl vinyl copolymer alcohol and maleic acid, 0.05-0.26 wt.% sodium fluoride, as well as acceptable carriers and excipients, including a polymer thickener, emulsifier, flavoring agent, sorbitol 70%, demineralized water, is stable in relation to the enzyme activity during long-term storage , while the activity of these enzymes, prepared in the form of a solution, decreases rapidly. Therefore, the claimed composition can be used for remineralization of hard tooth tissues and effective prevention of inflammatory periodontal diseases.

The present invention is illustrated by the following examples.

EXAMPLE 1

Composition in the form of a non-abrasive toothpaste based on lysine, papain, dextranase, alpha-amylase, glucoamylase, superoxide dismutase, glucose oxidase, lactoperoxidase or peroxidase, invertase, cytochrome c-oxidase, sphagnum extract, dipotassium azinase, calcium nitrate pyrrolidone carboxylate N-cocoyl ethylarginate; sodium-calcium salt of a copolymer of polymethyl vinyl alcohol and maleic acid; sodium fluoride and acceptable carriers or excipients has the following composition:

Lysine 0.01 Papain 0.01 Dextranase 0.01 Alpha amylase 0.01 Glucoamylase 0.01 Superoxide dismutase 0.01 Glucose oxidase 0.01 Lactoperoxidase 0.01 Invertase 0.01 Cytochrome c oxidase 0.01 Betaine 0.01 Sphagnum extract 0.01 Dipotassium glycyrrhizinate 0.01 Potassium thiocyanate 0.01 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01 Sodium Fluoride 0.05 Sodium-calcium salt of the copolymer polymethyl vinyl alcohol and maleic acid 0.01 Sodium carboxymethyl cellulose 0.50 Emulsifier 0.01 Flavoring 0.01 Sorbitol 70% 5.00 Demineralized water Rest

The specified composition is prepared according to the following method. All components except sodium carboxymethyl cellulose are successively dissolved in demineralized water, then sodium carboxymethyl cellulose is added and mixed until a gel forms. The resulting gel is stirred, vacuum and homogenized.

EXAMPLE 2

Composition in the form of a toothpaste based on hydroxis, lysine, papain, dextranase, alpha-amylase, glucoamylase, superoxide dismutase, glucose oxidase, lactoperoxidase or peroxidase, invertase, cytochrome c-oxidase, thuya extract, dipotassium glycyrrhizin, calcipotassium glycyrrhizin, -pyrrolidone carboxylate N-cocoyl ethylarginate; sodium-calcium salt of a copolymer of polymethyl vinyl alcohol and maleic acid; sodium fluoride and acceptable carriers or excipients has the following composition:

Hydroxysomes ™ 5.00 Lysine 5.00 Papain 5.00 Dextranase 5.00 Alpha amylase 5.00 Glucoamylase 5.00 Superoxide dismutase 5.00 Glucose oxidase 5.00 Peroxidase 5.00 Invertase 5.00 Cytochrome c oxidase 5.00 Betaine 5.00 Thuja extract 5.00 Dipotassium glycyrrhizinate 5.00 Potassium thiocyanate 0.50 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 5.00 Sodium Fluoride 0.26 Sodium-calcium salt of the copolymer polymethyl vinyl alcohol and maleic acid 5.00 Xanthan gum 0.70 Emulsifier 5.00 Flavoring 1.00 Sorbitol 70% 10.00 Demineralized water Rest

The specified composition is prepared according to the following method. All components except xanthan gum and hydroxis are successively dissolved in demineralized water, then xanthan gum and hydroxisomes are added and mixed until a paste forms. The resulting paste is mixed, vacuum and homogenized.

EXAMPLE 3

Composition in the form of a toothpaste based on hydroxyapatite, lysine, papain, dextranase, alpha-amylase, glucoamylase, superoxide dismutase, glucose oxidase, lactoperoxidase or peroxidase, invertase, cytochrome c-oxidase, thuja extract, dipotassium glycyrrhizin, calcium nitrate -pyrrolidone carboxylate N-cocoyl ethylarginate; sodium-calcium salt of a copolymer of polymethyl vinyl alcohol and maleic acid; sodium fluoride and acceptable carriers or excipients has the following composition:

Hydroxyapatite 5.00 Lysine 5.00 Papain 5.00 Dextranase 5.00 Alpha amylase 5.00 Glucoamylase 5.00 Superoxide dismutase 5.00 Glucose oxidase 5.00 Peroxidase 5.00 Invertase 5.00 Cytochrome c oxidase 5.00 Betaine 5.00 Thuja extract 5.00 Dipotassium glycyrrhizinate 5.00 Potassium thiocyanate 0.50 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 5.00 Sodium Fluoride 0.26 Sodium-calcium salt of the copolymer polymethyl vinyl alcohol and maleic acid 5.00 Carrageenan 0.70 Emulsifier 5.00 Flavoring 1.00 Sorbitol 70% 10.00 Demineralized water Rest

The specified composition is prepared according to the following method. All components except carrageenan and hydroxyapatite are successively dissolved in demineralized water, then carrageenan and hydroxyapatite are added and mixed until a paste forms. The resulting paste is mixed, vacuum and homogenized.

Evaluation of the stability of enzymes in topical compositions

Since the main disadvantage of enzymes is their instability during long-term storage of finished forms based on them during the expiration date, a comparative assessment was made of the preservation of the activity of the enzyme during storage in the form of a solution and in the form of a composition for local use.

Papain activity was determined by the following methods.

To determine the proteolytic activity of papain, a modified Kunitz method was used. Such a quantity of an enzyme is taken as one proteolytic unit, upon exposure to which casein on the substrate for 10 minutes under standard conditions, such a quantity of hydrolysis products is released that leads to an increase in optical density at a wavelength of 280 nm per unit.

To quantify papain, the Lowry method was used. The determination method is based on the fact that proteins with copper salts in an alkaline medium restore Follin's reagent. A Coomassie G-250 dye solution was prepared as follows: 100 mg of the dye was dissolved in 100 ml of phosphoric acid, diluted 5 times with water, then filtered through a thick paper filter. To determine the concentration in the sample, an equal volume of dye was added, mixed and the absorbance of the solution was measured at a wavelength of 595 nm.

The results are shown in the following table.

As can be seen from the table 1, the introduction of enzymes in the composition for topical application allows you to get stable cosmetic compositions for topical use in the prevention of inflammatory periodontal diseases. Despite the fact that upon the introduction of enzymes into the composition of such compositions, a slight loss of enzymatic activity occurs, upon further storage for 1 year, the enzymes do not change their activity due to the fixation of the labile structure of the enzyme by the carrier polymer.

The antimicrobial activity of D, L-pyrrolidone carboxylate N-cocoyl ethylarginate was determined by serial dilution. As a nutrient medium used meat-peptone broth; as test microorganisms, pure cultures: Staphylococcus aureus, Bacillus cereus, Esherichia coli, Candida albicans. A one-day culture of 1000 cells / ml was added to each tube. Cell cultures: Staphylococcus aureus, Bacillus cereus, and Esherichia coli were grown in test tubes in a medium with meat and peptone broth at 37 ° C for 24 hours, and a Candida albicans culture on Saburo agarized seldure at 24 ° C for two days. Titration was started at a concentration of 10 mg / ml (1/10 dilution). As a control, a test tube was used, into which only nutrient medium and microorganism were introduced. The concentration in the last tube with no growth was taken as the minimum inhibitory concentration. To assess the bactericidal effect of the tubes with a lack of growth, reseeding was done on plates with meat and peptone broth. The cups were thermostated at 37 ° C for a day. Bactericidal action was noted in the absence of growth on a solid nutrient medium.

As can be seen from table 2, the optimal inhibitory concentration is: for D, L-pyrrolidone carboxylate N-cocoyl ethylarginate: 5 mg / ml in the case of Staphylococcus aureus, Bacillus cereus, Escherichia coli; 1 mg / ml - for Candida albicans; bactericidal concentration for D, L-pyrrolidone carboxylate N-cocoyl ethylarginate - 10 mg / ml in the case of Staphylococcus aureus, Bacillus cereus, Escherichia coli; 20 mg / ml - for Candida albicans.

Clinical trials of the proposed toothpaste were carried out for one month on 30 volunteers aged 21-24 years old, clinically healthy, without deformation of the teeth and jaws. To determine the cleaning effect of the paste, controlled and uncontrolled brushing of the teeth by the proposed paste was carried out. The controlled brushing of the teeth was carried out according to the method proposed in the “Methodological guidelines for experimental (pharmacological) and clinical trials of preventive and therapeutic toothpastes” (Moscow-Sofia, 1983), for 3 minutes on the 1st, 7th, 14th th, 21st and 28-1 day. On the remaining days, probants brushed their teeth with the same brush and paste, morning and evening, at home without control. Before and after controlled cleaning, a Green-Vermillion hygiene index was determined:

Quantitative assessment was carried out according to a 4-point system:

- staining of the entire surface of the tooth crown was evaluated at 3 points;

- staining 2/3 of the surface of the tooth crown was evaluated at 2 points;

- staining 1/3 of the surface of the tooth crown was evaluated at 1 point;

- the absence of staining of the surfaces of the teeth was evaluated at 0 points.

The calculation of the hygiene index indicators according to Green-Vermillion was carried out according to the formula:

K _av = K / n, where

K _cp is the averaged digital indicator of the hygiene index for all teeth in which index indicators were determined;

K is the total sum of the index values for all teeth in which indicators were evaluated;

n is the number of teeth that were evaluated.

The cleaning effectiveness of toothpaste was calculated by the formula:

Purifying efficiency = [(IG up to _1- IG up to _X ) / IG up to ₁ ] × 100, where

IG _do1 - an indicator of the hygiene index obtained during the initial examination, before brushing your teeth;

IG _doX is an indicator of the hygiene index obtained during a subsequent examination (7, 14, 21, 28 days of examination), before brushing your teeth.

Plaque reduction during a single brushing was determined by the formula for each controlled brushing:

Reduction = [(IG _doX- IG _afterX ) / IG _doX ] × 100, where

IG _doX - an indicator of the hygiene index obtained during examination before the start of controlled brushing (1, 7, 14, 21, 28 days);

IG _afterX is an indicator of the hygiene index obtained during examination after conducting controlled brushing of teeth (1, 7, 14, 21, 28 days).

From the table. 3, 4 and 5 it can be seen that the proposed toothpaste has an increased cleaning ability, and hence the anti-caries effect due to a more pronounced removal of dental plaque and provides the removal of 62.06% of plaque.

To determine the anti-inflammatory properties of the proposed toothpaste, all the probants (the same 30 people) carried out controlled brushing for one month.

The anti-inflammatory effect of the paste was evaluated by changing the state of the gums attached to the teeth using the PMA index according to the formula:

PMA index = [Sum of indicators / (3 × number of teeth)] × 100, where

P - inflammation of the gingival papilla, which is estimated at 1 point;

M - inflammation of the gingival margin, which is estimated at 2 points;

A - inflammation of the attached gum of the alveolar process, which is estimated at 3 points.

Evaluation of the anti-inflammatory effect of toothpaste was carried out on the basis of an analysis of the dynamics of the PMA index, which was determined during repeated examinations on the 1st, 7th, 14th, 21st and 28th days. Anti-inflammatory efficacy was calculated by the formula:

Anti-inflammatory efficacy = [(PMA ₁ -PMA _x ) / PMA ₁ ] × 100, where

PMA ₁ - an indicator of the PMA index obtained during the initial examination on the 1st day of the study;

PMA _x is the index of PMA obtained during a subsequent examination (7, 14, 21 and 28 days).

The data are given in table. 6 and 7. It can be clearly seen from them that after using this paste, the condition of periodontal tissues improved significantly: 100% of the probans disappeared from catarrhal gingivitis, and the PMA index decreased from 57.1 to 8.5, which corresponded to 85.11% anti-inflammatory effectiveness this paste.

Assessment of hemostatic effect was carried out according to the index of hemorrhage Kechke:

I degree - rarely, estimated at 2 points;

II degree - during brushing, estimated at 4 points;

III degree - with meals and spontaneously, is estimated at 8 points.

Hemostatic effectiveness was determined by the formula:

Hemostatic effectiveness = [(IR ₁ -IR _x ) / IR ₁ ] × 100, where

IK ₁ - bleeding index at the beginning of the study;

IR _x is the bleeding index at the end of the experiment.

The data are given in table. 8 and 9. It can be seen from them that after using this paste, the condition of periodontal tissues improves, and the bleeding of the gums decreases from 4.7 to 1.3 points, which corresponds to 72.34% of the hemostatic effectiveness of this paste.

Thus, the proposed toothpaste has a higher cleansing (62.06% cleansing effectiveness), anti-inflammatory (85.11% anti-inflammatory effect) and hemostatic (72.34% hemostatic effectiveness) effect.

Table 11 summarizes the results of determining the remineralizing efficacy of the TER test.

The proposed means of oral hygiene also has a remineralizing effect due to the fact that there is a more active cleaning of the surfaces of the teeth and the mineral components of the oral fluid are able to more effectively penetrate the surface layer of enamel and form a protective layer of CaF ₂ .

Claims (3)

1. Toothpaste, characterized in that it contains: 0.01-5.0 wt.% Lysine, 0.01-5.0 wt.% Papain, 0.01-5.0 wt.% Dextranase, 0.01 -5.0 wt.% Alpha-amylase, 0.01-5.0 wt.% Glucoamylase, 0.01-5.0 wt.% Superoxide dismutase, 0.01-5.0 wt.% Glucose oxidase, 0.01 -5.0 wt.% Lactoperoxidase or peroxidase, 0.01-5.0 wt.% Invertase, 0.01-5.0 wt.% Cytochrome c-oxidase, 0.01-5.0 wt.% Sphagnum extract or thuja, 0.01-5.0 wt.% dipotassium glycyrrhizinate, 0.01-0.5 wt.% potassium thiocyanate, 0.01-5.0 wt.% betaine, 0.01-5.0 wt. % D, L-pyrrolidone carboxylate N-cocoyl ethyl arginate, 0.01-5.00 wt.% Sodium-calcium salt of the copolymer polymer lvinilovogo alcohol and maleic acid 0,05-0,26 wt.% of sodium fluoride, as well as acceptable carriers and excipients including polymeric thickener, emulsifier, flavor, sorbitol 70% demineralised water. 2. Toothpaste according to claim 1, characterized in that it has the following composition in the following ratio of components, wt.%:
Lysine 0.01-5.00 Papain 0.01-5.00 Dextranase 0.01-5.00 Alpha amylase 0.01-5.00 Glucoamylase 0.01-5.00 Superoxide dismutase 0.01-5.00 Glucose oxidase 0.01-5.00 Lactoperoxidase 0.01-5.00 Invertase 0.01-5.00 Cytochrome c oxidase 0.01-5.00 Betaine 0.01-5.00 Sphagnum extract 0.01-5.00 Dipotassium glycyrrhizinate 0.01-5.00 Potassium thiocyanate 0.01-0.50 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01-5.00 Sodium Fluoride 0.05-0.26 Sodium-calcium salt of the copolymer polymethyl vinyl alcohol and maleic acid 0.01-5.00 Sodium carboxymethyl cellulose 0.50-0.70 Emulsifier 0.01-5.00 Flavoring 0.01-1.00 Sorbitol 70% 5.00-10.00 Demineralized water Rest 3. Toothpaste according to claim 1, characterized in that it has the following composition in the following ratio of components, wt.%:
Hydroxyapatite 0.01-5.00 Lysine 0.01-5.00 Papain 0.01-5.00 Dextranase 0.01-5.00 Alpha amylase 0.01-5.00 Glucoamylase 0.01-5.00 Superoxide dismutase 0.01-5.00 Glucose oxidase 0.01-5.00 Peroxidase 0.01-5.00 Invertase 0.01-5.00 Cytochrome c oxidase 0.01-5.00 Betaine 0.01-5.00 Sphagnum extract 0.01-5.00 Dipotassium glycyrrhizinate 0.01-5.00 Potassium thiocyanate 0.01-0.50 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01-5.00 Sodium Fluoride 0.05-0.26 Sodium-calcium salt of the copolymer polymethyl vinyl alcohol and maleic acid 0.01-5.00 Carrageenan 0.50-0.70 Emulsifier 0.01-5.00 Flavoring 0.01-1.00 Sorbitol 70% 5.00-10.00 Demineralized water Rest 4. Toothpaste according to claim 1, characterized the fact that it has the following composition in the following ratio of components, wt.%: Hydroxysomes ™ 0.01-5.00 Lysine 0.01-5.00 Papain 0.01-5.00 Dextranase 0.01-5.00 Alpha amylase 0.01-5.00 Glucoamylase 0.01-5.00 Superoxide dismutase 0.01-5.00 Glucose oxidase 0.01-5.00 Peroxidase 0.01-5.00 Invertase 0.01-5.00 Cytochrome c oxidase 0.01-5.00 Betaine 0.01-5.00 Thuja extract 0.01-5.00 Dipotassium glycyrrhizinate 0.01-5.00 Potassium thiocyanate 0.01-0.50 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01-5.00 Sodium Fluoride 0.05-0.26 Sodium-calcium salt of the copolymer polymethyl vinyl alcohol and maleic acid 0.01-5.00 Xanthan gum 0.50-0.70 Emulsifier 0.01-5.00 Flavoring 0.01-1.00 Sorbitol 70% 5.00-10.00 Demineralized water Rest