WO2019190347A1 - Composition pour le blanchiment de dents - Google Patents

Composition pour le blanchiment de dents Download PDF

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Publication number
WO2019190347A1
WO2019190347A1 PCT/RU2018/000434 RU2018000434W WO2019190347A1 WO 2019190347 A1 WO2019190347 A1 WO 2019190347A1 RU 2018000434 W RU2018000434 W RU 2018000434W WO 2019190347 A1 WO2019190347 A1 WO 2019190347A1
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Prior art keywords
composition
whitening
enamel
enzymes
phosphates
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PCT/RU2018/000434
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English (en)
Russian (ru)
Inventor
Светлана Анатольевна ЗАКИРОВА
Павел Павлович НЕСМИЯНОВ
Ирина Евгеньевна ЯГАФАРОВА
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Общество с ограниченной ответственностью "СПЛАТ-КОСМЕТИКА"
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Publication of WO2019190347A1 publication Critical patent/WO2019190347A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/66—Enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59—Mixtures
    • A61K2800/592—Mixtures of compounds complementing their respective functions
    • A61K2800/5922—At least two compounds being classified in the same subclass of A61K8/18

Definitions

  • the causes of disco- loritis can be the effects of internal factors: staining of teeth with hereditary lesions, systemic lesions, with the use of certain medications during odontogenesis, with lesions of the tooth pulp, under the influence of iatrogenic factors, etc. [2].
  • Enamel discoloration may occur due to the activity of various bacteria. So, S. Mutans form a plaque biofilm to which various chromophores are already attached. Actinomycetes, in turn, produce hydrogen sulfide, which, after reaction with iron cations in saliva, forms an insoluble precipitate of black ferrous sulfide. Serratia marcescens, Flavobacterium lutescens are less common, they are present in the oral cavity in only 3% of the population, leading to the formation of an orange plaque [19].
  • enamel can acquire a hue due to the penetration of various metals into the pellicle.
  • the presence of copper leads to a greenish tint of enamel [20].
  • the most complex in nature are pigments, which are formed as a result of the Mayair reaction.
  • Such reactions include the interaction of amino acids and sugars when heated, for example, in the process of roasting coffee beans.
  • dark colored products are formed, indicating the occurrence of the Maillard reaction.
  • Enzymatic bleaching methods have a significant advantage, as they are safe for enamel and do not lead to its destruction, but the optimal composition of enzymes in products known on the market does not yet exist.
  • enzymatic methods that relate to gentle enamel whitening, several oral care inventions are known. However, most of these developments are aimed at breaking down protein plaque or protecting against caries.
  • bleaching systems the main active component of which would be enzymes, do not exist. For example, papain and bromelain break down protein plaque, but they do not bleach pigments that penetrate deeper into enamel, which necessitates the use of other bleaching agents, such as peroxides.
  • compositions are aimed at the complex cleavage of plaque and tartar in combination with a whitening effect, which leads to the need to use incompatible components.
  • proteolytic enzymes and any components of a protein nature for example, amylase, cellulase, xylanase enzymes
  • the simultaneous use of proteolytic enzymes and any components of a protein nature leads to the destruction of the latter, since proteolytic enzymes break down proteins to short peptides and amino acid residues.
  • all developments aimed at the simultaneous cleavage of protein and polysaccharide plaque turn out to be ineffective, since enzymes that break down polysaccharide plaque are of a protein nature.
  • inventions that seek to achieve the whitening effect act due to the splitting of the bacterial plaque, which can again form, which eliminates the whitening effect.
  • some of the patented complexes contain components that are incompatible with the components of toothpastes.
  • the simultaneous introduction of a carboxymethyl cellulose thickener and a cellulase enzyme leads to the destruction of the thickener, since this enzyme has substrate specificity for celluloses. This can lead to a decrease in the activity of the enzyme in the finished product, since part of it will be spent on a chemical reaction with a thickener.
  • a two-component composition of a dentifrice having an increased antibacterial effectiveness.
  • Enzymes that can be used in the implementation of the disclosed composition include enzymes extracted from natural fruit products, such as well-known protein substances within the class of proteases, which break down or hydrolyze proteins.
  • Proteolytic enzymes are obtained from natural sources or by the action of microorganisms having a nitrogen source and a carbon source. Examples of proteolytic enzymes that can be used in the practice of the present invention include naturally occurring enzymes papain (from papaya), bromelain (from pineapple), as well as serine proteases, such as chymotrypsin.
  • Additional enzymes include ficin and alkalase.
  • Papain derived from the papaya tree’s milky sap is a proteolytic enzyme preferred for use in the open composition.
  • Enzymes that can be used in combination with proteolytic enzymes include carbohydrases, such as glucoamylase, alpha-amylase, beta-amylase, dextranase and mutanase, tannase, and lipases, such as plant lipase, gastric lipase, and pancreatic lipase.
  • carbohydrases such as glucoamylase, alpha-amylase, beta-amylase, dextranase and mutanase, tannase
  • lipases such as plant lipase, gastric lipase, and pancreatic lipase.
  • the disadvantage of this invention is the use of proteolytic enzymes in conjunction with carbohydraz class enzymes.
  • Proteolytic enzymes destroy
  • this invention contains components that inhibit the action of each other, which leads to a decrease or complete lack of effectiveness of the use of this composition.
  • the patent proposes the use of the glucoamylase enzyme, which does not have the ability to cleave polysaccharide molecules, since alpha amylase must be used for these purposes. It is also proposed to use tin salts in the composition, in particular tin fluoride, and it has a coloring effect on enamel.
  • EP2298904A1 publ. 23.03.2011
  • xylanases and the possibility of their use in dentifrices such as toothpastes, tooth creams, gels or tooth powders, means for washing the mouth, chewing gum, lollipops or candies.
  • EP2280686A1 (publ. 23.03.2011) a-glucanases and the possibility of their use in dentifrices for preventing or reducing plaque are disclosed.
  • the use of a-glucanases leads to a decrease in plaque, but since many chromogens penetrate deep into the enamel, it is not enough to get rid of polysaccharide plaque alone to obtain a whitening effect.
  • the disadvantage of this invention is the targeted cleavage of only 1,6-a-glucoside bonds of dextran, and the polysaccharide coating consists of a mixture of polysaccharides (intracellular, consisting mainly of reserve polymers such as glycogen, amidopectin, and extracellular, which are dextrins and levanes), and for effective cleavage of plaque, it is necessary to use components that destroy all bonds of the polysaccharide matrix.
  • the famous line of HappyDent toothpastes (At Krajina) (“Toothpastes for adults without fluoride”, on-line, ⁇ URL: http: //www.happy- dent.pro/ru/products/toothpastes_without_fluoride>), containing Amilolin® - a combination of the natural enzyme Amilosubtilin, a vitamin complex (B, C, E, PP, K, A vitamins) and minerals.
  • the natural enzyme Amilosubtilin is a complex of enzymes (alpha-amylase, neutral and slightly alkaline proteinases, beta-glucanase, cellulase, xylanase), which prevent the formation of plaque and stone. Enzymes have a cleansing effect on the oral cavity, promote the breakdown of protein plaque.
  • the simultaneous combination of proteases and hydrolases leads to the destruction of the latter due to their protein nature; as a result, the complex loses its effectiveness in the formulation of toothpaste.
  • the enzyme papain promotes the breakdown of protein plaque, but does not destroy enamel-staining melanoidins.
  • the newly developed whitening complex can significantly overcome the above-described disadvantages and is aimed at clarifying the products of the Maillard reaction, one of the products of which are melanoidins, which give a stable color to tooth enamel [18].
  • the present invention relates to a composition for use in an oral composition comprising a combination of pectinase, xylanase and b-glucanase enzymes.
  • composition of the invention may further comprise a filler.
  • composition of the invention may contain 0.05-0.15% by weight of pectinase, 0.05-0.15% of May. xylanases, 0.01-0.05% of May. beta-glucanases and up to 100% of May. filler.
  • composition of the invention may contain about 0.2% by weight of pectinase, about 0.2% of May. xylanase, about 0.1% in May. beta-glucanases and up to 100% of May. filler.
  • composition of the invention may contain 0.1-1.0% by weight pectinase, 0, 1-1, 0% May. xylanase, 0.05-0.6% in May. beta-glucanases and up to 100% of May. filler.
  • composition of the invention further comprises phosphates: calcium glycerophosphate, calcium pyrophosphate, tetra potassium pyrophosphate, tetrasodium pyrophosphate, disodium pyrophosphate, tricalcium phosphate, trimagnesium phosphate, sodium tripolyphosphate, sodium hexametaphosphate.
  • phosphates calcium glycerophosphate, calcium pyrophosphate, tetra potassium pyrophosphate, tetrasodium pyrophosphate, disodium pyrophosphate, tricalcium phosphate, trimagnesium phosphate, sodium tripolyphosphate, sodium hexametaphosphate.
  • phosphates are contained in the composition in an amount of 0.5-4.5% in May.
  • phosphates are contained in the composition in an amount of 0.5-3.0% in May.
  • phosphates are contained in the composition in an amount of 0.5-1.0% May.
  • the present invention also relates to a toothpaste containing the composition of the invention.
  • the present invention also relates to an oral rinse containing the composition of the invention.
  • the present invention also relates to the use of a composition of the invention for whitening teeth.
  • the present invention also relates to the use of the toothpaste of the invention for whitening teeth.
  • the present invention also relates to the use of the rinse aid of the invention for whitening teeth.
  • the claimed complex tooth whitening agent contains a combination of enzymes of the pectinase, xylanase and b-glucanase groups.
  • Pectinase is a general term for pectin-cleaving enzymes. Includes pectoliasis, pectosis and polygalacturonase. It belongs to a heterogeneous group of enzymes that catalyze the degradation of pectin. In the composition of pectinases, the following groups of enzymes can be distinguished:
  • Pectin esterases catalyze the elimination of pectin methyl groups to form pectic acid.
  • Polygalacturonases (enzyme class 3.2.1.15) hydrolyze a-1,4-glycosidic bonds in a chain of pectin substances. They are divided into polymethylgalacturonases (act on pectin) and polygalactronases (act on pectic acid).
  • Pectolytic preparations are divided into two groups depending on the pH optimum of enzyme activity: acidic and alkaline. These properties determine the possibility of using pectinases for various industries. Acid pectinases are used in the production of juices and wines, and alkaline pectinases are used in the textile industry.
  • Pectinases obtained with the help of fungal strains of producers are active at acidic pH values, while alkaline enzymes are produced by bacterial strains.
  • the most common technology is the production of pectinase from Aspergillus niger using methods of deep and surface cultivation. It is noted that the use of solid-phase fermentation methods for the cultivation of fungal producer strains allows one to obtain a high yield of concentrated pectinases at a lower cost than with deep fermentation. Cultivation conditions using the surface cultivation method are most optimal for the growth of Aspergillus sp. To obtain bacterial pectinases, both cultivation methods are used.
  • Xylanase is a general term for enzymes involved in the degradation of a heterogeneous polysaccharide, xylan.
  • the main enzyme is endo-1,4-xylanase (enzyme class 3.2.1.8), which catalyzes the decomposition of xylan to xylo-oligosaccharides.
  • Other enzymes such as xylosidase, b-arabinofurazidase, glucuronidase and esterase (xylanacetyl esterase and feryloyl esterase) perform the complete hydrolysis of xyloligosaccharides to monomers.
  • Xylanases are glycoproteins with a molecular weight of 6-80 kDa. Enzymes are active in the temperature range 40-60 ° C and pH 4, 5-6, 5. [24].
  • b-Glucanase (beta-glucanase) is a generic term for enzymes that break down non-starch polysaccharides (LCPs) of hemicelluloses (glucans). It belongs to the group of enzymes catalyzing the cleavage of b-glucans with b-1,2-, b-1,3-, b-1,4- and b-1,6-bonds. All b-glucanases are acidic proteins containing a large number of carboxyl and hydroxyl groups. These enzymes are glycoproteins; they have carbohydrate fragments containing residues of mannose, glucose, galactose [25]. Trichoderma, Aspergillus, Penicillium, Bacillus, etc. are used as producer strains in the production of beta-glucanase.
  • the combination of pectinase, xylanase and beta-typucanase in the composition for the oral cavity has certain advantages: effective splitting of melanoidin molecules, safe whitening.
  • the invention makes it possible to safely clarify tooth enamel by targetedly affecting enamel-staining melanoidins.
  • the proposed complex is capable of cleaving unpolished polysaccharide plaque, thereby preventing the formation of a cariogenic biofilm, which is a prevention of caries prevention.
  • the inventors also unexpectedly found that the additional use of a component from phosphate groups enhances the whitening effect of the enzymatic complex (synergism).
  • the invention relates to a composition for use in an oral composition comprising a combination of pectinase, xylanase and b-glucanase enzymes.
  • composition of the invention may further comprise an excipient.
  • a composition of the invention may comprise 0.05-0.15% May. pectinases, 0.05-0.15% of May. xylanases, 0.01-0.05% of May. beta-glucanases and up to 100% of May. filler.
  • the composition according to the invention may contain about 0.1% by weight of pectinase, about 0.1% of May. xylanase, about 0.025% wt. beta-glucanases and up to 100% of May. filler.
  • a composition of the invention may comprise about 0.2% by weight pectinase, about 0.2% May. xylanase, about 0.1% wt. beta-glucanases and up to 100% of May. filler.
  • a composition of the invention may comprise 0.1-1.0% by weight pectinase, 0.1-1.0% by weight. xylanase, 0.05-0.6% wt. beta-glucanases and up to 100% of May. filler.
  • the composition according to the invention may contain 0, 3-0, 8% wt. Pectinase, 0.3-0, 8% wt. xylanase, 0.2-0, 4% of May. beta-glucanases and up to 100% of May. filler.
  • the composition of the invention may contain 0.5% by weight pectinase, 0.5% May. xylanase, 0.3% in May. beta-glucanases and up to 100% of May. filler.
  • the composition of the invention further comprises phosphates that may be selected from the group: phosphates: calcium glycerophosphate, calcium pyrophosphate, tetracal potassium and tetrasodium pyrophosphate, as well as disodium pyrophosphate, tricalcium and trimagnesium phosphates, tripolyphosphate sodium, hexametha-sodium phosphate.
  • phosphates may be selected from the group: phosphates: calcium glycerophosphate, calcium pyrophosphate, tetracal potassium and tetrasodium pyrophosphate, as well as disodium pyrophosphate, tricalcium and trimagnesium phosphates, tripolyphosphate sodium, hexametha-sodium phosphate.
  • phosphates are contained in the composition in an amount of 0.5-4.5% May.
  • the phosphates may be contained in the composition in the amount of 2.5-3.0% in May.
  • the phosphates may be contained in the composition in an amount of about 2.75% May.
  • phosphates are contained in the composition in an amount of 0.5-3.0% May.
  • the phosphates may be contained in the composition in an amount of 1.5-2.5% of May. More preferably, phosphates may be contained in the composition in an amount of about 2.0% in May.
  • phosphates are contained in the composition in an amount of 0.5-1.0% May.
  • the phosphates may be contained in the composition in an amount of 0.6-0, 9% May. More preferably, phosphates may be contained in the composition in an amount of about 0.75% May.
  • the invention also relates to a toothpaste containing the composition of the invention.
  • the invention also relates to a mouthwash containing the composition of the invention.
  • the invention also relates to the use of a composition according to the invention for tooth whitening.
  • the invention also relates to the use of the toothpaste according to the invention for whitening teeth.
  • the invention also relates to the use of a rinsing agent according to the invention for tooth whitening.
  • Example 1 Proof of the effectiveness of the components of the complex in vitro. Evidence of the effectiveness of the complex was carried out on stained samples imitating tooth enamel. Initially, samples imitating tooth enamel were prepared, then they were artificially stained with a saturated solution of tea and coffee. For this, 40 g of roasted coffee beans were ground to a powder state, 50 ml of water heated to 96 ° C were added, and stirred for 10 minutes. Then the resulting mixture was filtered, and 50 ml of water heated to 99 ° C was added to the precipitate, and stirred for another 10 minutes. After filtering off the precipitate, both filtrates were combined.
  • a high-grade coffee solution was obtained in which the samples were placed (one sample was left unpainted for control) for 24 hours at a temperature of 25 ° C.
  • 20 g of ground black tea (not aromatized) were placed in a clean glass and 100 ml of water heated to 99 ° C was added. It was left for 20 minutes with constant stirring, then it was filtered off and samples were added to the filtrate (one sample was left unpainted for control) for staining for 24 hours at a temperature of 25 ° C. After staining, the samples were washed under running water, dried and photographed to obtain initial staining brightness values.
  • 51.0 ml of 27.2 g / l potassium dihydrogen phosphate solution was mixed with 49.0 ml of 71.6 g / l disodium hydrogen phosphate solution.
  • the resulting solution was stored at a temperature of 2 to 8 ° C.
  • Example 2 The study of the comparative effectiveness of an in vitro enzymatic complex with known bleaching systems. The selected components of the complex have a joint whitening effect, therefore, the authors compared the developed bleaching complex with peroxide systems with high whitening efficiency. Table 3 shows the groups for comparing the whitening activity.
  • One coffee-coated sample C) was placed in 30 ml of buffer IV, and another tea-coated (T) sample was placed in another glass with 30 ml of buffer IV.
  • Three samples (C and T) were placed in different glasses in 100 ml of 3% solution III and in different glasses in 100 ml of solution III so that the samples did not come into contact with each other.
  • 3 samples of different types of staining were placed in 100 ml of a solution of the enzymatic complex I.
  • the glasses were covered with filter paper or glass to prevent dust and other contaminants.
  • Three samples were placed in a suspension of toothpaste II (three samples C and 7), tightly closed with a lid to prevent drying of the toothpaste. All samples were incubated at 37 ° C for 6 hours.
  • Example 3 Evidence of the in vitro whitening efficacy of an enzymatic complex in oral care compositions.
  • a toothpaste formulation with an enzymatic complex (1) a formulation with an enzymatic complex and calcium pyrophosphate (2), a basic formulation that does not contain bleaching components (3) were developed. Samples were stained similarly to Example 1 (Tables 5-7).
  • Table 7 The composition of the base composition of the studied composition for caring for the oral cavity that does not contain active whitening components
  • Example 4 Evidence of the in vivo whitening efficacy of an enzyme complex in oral care compositions. For clinical trials, the formulation of products containing the enzymatic complex was developed (Table 9).
  • the number of teeth is at least 20.
  • the maximum duration of participation in the study for each volunteer was 31 days.
  • the minimum duration of participation in the study for each subject was 25 days. Volunteers used 1 product for a visit for 2 minutes. Further, patients used the test products 2 times a day for 2 minutes, morning and evening, for 4 weeks with an intermediate visit to the dentist on the 14th day of the study. Before and after application of the product, 6 upper front teeth were evaluated on a Vita scale (Table 10).
  • Tooth discolouration and staining Tooth discolouration and staining: a revision of the literature. British Dental Journal, 2001; 190: 309 - 316.
  • Calcium glycerophosphate supplemented to soft drinks reduces bovine enamel erosion; Carolina Silveira Barbosa; Lia Guimaraes Montagnolli; Melissa Thiemi Kato; Fabio Correia Sampaio; Marilia Afonso Rabelo Buzalaf; J. Appl. Oral Sci. vol.20 no.4 Bauru July / Aug. 2012
  • ACP amorphous calcium phosphate

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oral & Maxillofacial Surgery (AREA)
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  • Epidemiology (AREA)
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Abstract

L'invention concerne une composition à utiliser dans la cavité buccale qui comprend une combinaison de ferments pectinase, xylanase, β-glucanase ainsi qu'un dentifrice et un produit de rinçage de bouche les contenant. La composition, le dentifrice et le produit de rinçage de bouche peuvent s'utiliser pour le blanchissement de l'émail dentaire. L'invention permet de blanchir l'émail dentaire en toute sécurité par l'action directe sur les mélanoïdine qui colorent l'émail dentaire.
PCT/RU2018/000434 2018-03-28 2018-06-29 Composition pour le blanchiment de dents WO2019190347A1 (fr)

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US20050136162A1 (en) * 2001-10-04 2005-06-23 Kvist Sten U. Process for the fractionation of oilseed press cakes and meals
KR20170001140A (ko) * 2015-06-25 2017-01-04 경희대학교 산학협력단 치면세균막 형성 억제용 조성물
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