WO2022216256A2 - Coquille d'oeuf et membrane de coquille d'oeuf contenant un vernis dentaire - Google Patents

Coquille d'oeuf et membrane de coquille d'oeuf contenant un vernis dentaire Download PDF

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WO2022216256A2
WO2022216256A2 PCT/TR2022/050250 TR2022050250W WO2022216256A2 WO 2022216256 A2 WO2022216256 A2 WO 2022216256A2 TR 2022050250 W TR2022050250 W TR 2022050250W WO 2022216256 A2 WO2022216256 A2 WO 2022216256A2
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eggshell
membrane
stmp
dental
adsorbed
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PCT/TR2022/050250
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WO2022216256A3 (fr
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Ilhami Celik
Ercan Durmus
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Imicryl Dis Malzemeleri Sanayi Ve Ticaret Anonim Sirketi̇
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Priority claimed from TR2021/006313 external-priority patent/TR2021006313A2/tr
Application filed by Imicryl Dis Malzemeleri Sanayi Ve Ticaret Anonim Sirketi̇ filed Critical Imicryl Dis Malzemeleri Sanayi Ve Ticaret Anonim Sirketi̇
Publication of WO2022216256A2 publication Critical patent/WO2022216256A2/fr
Publication of WO2022216256A3 publication Critical patent/WO2022216256A3/fr

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00Preparations for dentistry
    • A61K6/20Protective coatings for natural or artificial teeth, e.g. sealings, dye coatings or varnish
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K6/00Preparations for dentistry
    • A61K6/70Preparations for dentistry comprising inorganic additives
    • A61K6/71Fillers
    • A61K6/74Fillers comprising phosphorus-containing compounds

Definitions

  • the invention is related to a florine-free dental varnish, which is applied on the tooth surface to prevent development and progress of dental caries in demineralised enamel, on the other hand contributing alleviaton of gingival inflammations and regeneration of gingival lesions, not stimulating gag and split reflex with its aroma, hardening soon after appliying to the tooth surface, not causing allergic reactions and systemic or local toxications, not containing florine, containing micronized eggshell powder and tri-sodium tri-metaphosphate adsorbed eggshell membrane.
  • a dental caries begins with decay of the dental hard tissues by diffusing and demineralizing the mineralised matrix by organic acids resulted in bacterial metabolism. Development of the dental caries is a process that resulted in many demineralization-remineralization cycles. The development period of a dental caries is a process that occurs as a result of many demineralization-remineralization cycles.
  • Demineralization is arisen from the loss of calcium (Ca +2 ) ions, phosphate (P04 3 ) ions and other ions from the tooth under the influence of pathological factors that cause the dissolution of hydroxyapatite crystals.
  • the most important cause of demineralization of tooth enamel is decreasing the pH of the environment below the dissolution threshold of hydroxyapatite.
  • the progression or regression of dental caries depends on the critical balance between demineralization and remineralization processes in the tooth. It is very important for healthy teeth to maintain this balance, which is determined by the concentrations of Ca +2 and P04 3 ions in the saliva as well as the usable F _1 ion concentration in the environment, which ensures the formation of an undamaged enamel surface. Remineralization occurs when Ca +2 , P04 3 and F _1 ions form hydroxyapatite and fluorapatite crystals on the tooth enamel surface and lesion area at critical ambient pH. Mineral loss in incipient caries is inversely proportional to the saturation of the environment with Ca +2 and P04 -3 ions and ambient pH. The pH range for maintaining the remineralization and demineralization balance is 4.5-5.1 and prominent surface layers form in this range, while surface layers do not form around pH 6.0.
  • Remineralization applications which are performed at the initial stage of caries development, have received increasing attention in recent years as a non-invasive treatment with accepted therapeutic importance, and for this purpose, it is aimed to introduce many formulations with different efficacy levels.
  • Nano-sized n-HAP particles are morphologically and structurally similar to enamel hydroxyapatite. n-HAp is considered a biocompatible and bioactive substance. n-HAP, which was added to toothpastes and mouthwashes in many studies conducted in recent years, is thought to have a remineralization potential in initial caries lesions.
  • Nano-p-tricalcum phosphate (h-b-TCP) h-b-TCP is a substance that has the potential to be used for remineralization. It has been shown that the elastic modulus and mineral density of dentin after remineralization in tooth samples immersed in h-b-TCP solution are higher than those immersed in hydroxyapatite.
  • ACP Amorphous calcium phosphate
  • ACP is the initial solid phase that precipitates in a supersaturated calcium phosphate solution. Since it can easily transform into stable crystalline phases such as octacalcium phosphate or apatitic products, it is thought to play a role as a temporary phase in the formation of apatite in biomineralization.
  • the dentin surface is completely covered with hydroxyapatite crystals formed as a result of the application of calcium phosphate loaded agarose gel, and the dentin tubules are obstracted.
  • Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP)
  • the casein phosphopeptide in the CPP-ACP complex can provide calcium and phosphate ions necessary for the remineralization of the hard tissues of the tooth by stabilizing the amorphous ACP with its phosphoserine extensions.
  • CPP-ACP prevents demineralization on the healthy dentin surface and increases remineralization in artificial caries lesions created in dentin.
  • Ca2Si04 cements traditionally called mineral trioxide aggregate (MTA) are Portland derivative cements.
  • Ca2Si04 cements are the materials with bioactive behavior that promote the formation of apatite-containing tissues by releasing Ca +2 and OH 1 ions into the surrounding fluids in a short induction period. Therefore, the Ca2Si04 containing materials are used in the remineralization of demineralized dentin.
  • PAA Polyacrylic acid
  • DMP-1 Dentin Matrix Protein-1
  • PVPA forms analogs of DMPs, inhibits the activity of matrix metalloproteinases, binds ACP nanoprecursors to the collagen matrix and enables DMP-1 to bind to collagen.
  • PAMAM-NH2 The PAMAM with amine-terminal
  • PAMAM-NH2 Polyhydroxy- terminal PAMAM
  • PAMAM-OH Polyhydroxy- terminal PAMAM
  • PAMAM- COOH carboxy-terminal PAMAM
  • Agarose is a polyanionic polysaccharide containing repeating monomer units.
  • the anionic groups of agarose bind to the positively charged groups of collagen, allowing the growth of hydroxyapatite crystals.
  • it facilitates the transport of Ca +2 and PO4 3 ions to the dentin surface and the formation of hydroxyapatite crystals through directed ion diffusion.
  • the A-HG system also occludes open dentinal tubules and covers the remineralized dentin surface with an enamel-like tissue. Thus, it can reconstruct the microstructure of dentin.
  • L-GA has effects such as initiating and promoting remineralization, replacing DMP-1 with these substance-rich areas.
  • the remineralized dentin layer which is formed by the common effect of PAA and L-GA, has the same properties as natural dentin.
  • DMP-1 Dentin matrix protein-1
  • DMP-1 is a noncollagenous protein that largely regulates biomineralization in the dentin matrix. It stabilizes the Ca +2 and PO4 3 ions in the microenvironment by forming the precursor structures required for remineralization. In addition, ACP nanoparticles settle in the intrafiberlar region of the collagen and form apatite crystals in this region. It ensures crystal growth in the intrafiberlary spaces, increases the mechanical properties of dentin, and protects collagen from enzymatic and acidic destructions. A6.7. Phosphorylated chitosan (P-chi)
  • Phosphorylated chitosan which used in the biomimetic remineralization of dentin, has functions such as initiating remineralization and binding to collagen fibers and introducing the functional groups on it.
  • bioactive glasses are materials that have the potential to be used for remineralization in dentistry.
  • FHA-G Fluorohydroxyapatite gel
  • FHA gel system contains calcium nitrate (Ca(N03)2), potassium dihydrogen phosphate (KH2PO4), potassium fluoride (KF), deionized water and agarose. It is widely accepted that FFIA-G can form apatite structures on dentin in deep caries and encourage remineralization by diffusion of Ca +2 and PO4 '3 ions from A-FIG towards the dentin surface.
  • the most important ones of the main functional substances used in the preparation of traditional dental varnishes containing fluorine are the substances that act as a source of Ca +2 and PO4 '3 ions to be used in the remineralization area, and excipients substances including water, thickeners, viscosity increasers, pH buffers, sweeteners and flavorings.
  • DCP di-calcium phosphate
  • TCP tri calcium phosphate
  • BAG bioactive glass
  • F is the main functional component of conventional dental varnishes.
  • F has been used for 50 years as milk additive, salt, oral cleaning products and food supplements as local and systemic applications in order to prevent the formation and progression of dental caries.
  • this practice has been currently terminated in many countries since systemic toxications have emerged.
  • oral care products such as F-containing toothpastes, gels, mouthwashes have been prepared for this purpose.
  • F is also used to reduce dentin sensitivity. Fluorinated dental varnishes have been developed to increase the contact time of F with the tooth, thereby enhancing the penetration of the enamel into the surface layers.
  • the application of fluoride tooth varnish to 5-year-old-children has widely been used.
  • the app is also carried out in the disabled and weak people who are bedridden.
  • the fluorine tooth varnishes which are used for this purpose, contain about 5% topical fluoride (NaF) that a level relatively higher than those of toothpastes and and mouthwashes.
  • This application might increase F ratio of environment of the enamel surface up to 77%.
  • the producers recommend keeping away from foods and beverages for first 30 minutes and from hot and hard foodstuffs in the following 4 hours, not to brush teeth during the application day, and to start regular toothbrush at the day after. It is also recommended that the aplication should be repeated every 6 months.
  • the main content of fluorine varnishes is 5% NaF.
  • fluorine tooth varnish contributes to the formation of good quality enamel that is resistant to caries by ensuring the healthy development and well mineralization of the enamel layer of the developing tooth.
  • Topically applied F also replaces the OFF 1 ions in the hydroxyapatite crystal to form florapatite. It is accepted that fluorapatite is more difficult to dissolve and prevents the formation of acid in the microbial dental plaque on the tooth surface, preventing the dissolution of hydroxyapatite in the enamel and as a result supporting the remineralization of enamel.
  • Dental fluorosis which displays an increasing incidence, leads to mild to severe esthetic disorders and mineral substance losses in the teeth and requires restorative or prosthetic treatment.
  • acute fluoride toxicity may also develop, especially if large amount of the gel is swallowed.
  • the acute toxic dose of NaF is 5 mg/kg
  • 50 mg of NaF is the amount required for the occurence of acute toxic symptoms for a 10 kg child.
  • a toxic dose can be reached if a child of this weight swallows 4 ml of dental gel.
  • NaF used in oral care products has some allergic- immunological effects.
  • NaF can cause harmful effects not only on the oral mucosa, but also by reacting with hydrochloric acid in the stomach to form corrosive and non- dissociated hydrofluoric acid (HF). This acid also damages the gastro-duodenal mucosa.
  • Dental varnishes are coating materials in gel form that are applied as a thin layer on demineralized tooth surfaces with the help of a brush. Dental varnishes also contain hardener, thickener, flavoring agents and solvents.
  • the composition of dental varnish includes resins and thickeners. Hydrolysed-resin and partially hydrolyzed-resins are most preferred resins. Carboxy methylcellulose (CMC) and xanthan gum (Xsantan gum) are added to the formula as thickeners. Resin and thickeners provide film formation and mechanical stability on the tooth surface, and realize the controlled release of the functional substances of the varnish to the tooth surface.
  • CMC Carboxy methylcellulose
  • Xsantan gum xanthan gum
  • Solvents are also added into the dental varnish as a phase to increase the wettability of the surface, to guarantee the homogeneous mixing of the components and to carry the other components of the varnish.
  • the most commonly used solvent is ethyl alcohol.
  • Polyethylene glycol (PEG) is also added to dental varnishes in required amounts due to its high solubility and thickening properties.
  • NaHC03 sodium bicarbonate
  • the subject of the invention is related to dental varnish which the main components are micronized egg shell powder and sodium tri-metaphosphate (STMP) adsorbed egg shell membrane.
  • STMP sodium tri-metaphosphate
  • the eggshell mainly consists of calcium carbonate as the mineral part of the egg shell (98.4%).
  • the shell contains 0.8% of calcium carbonate nad 0.8% of tricalcium phosphate (TCP).
  • TCP tricalcium phosphate
  • Approximately 0.64% of the shell is protein, 1.7% is water and 0.03% is lipid.
  • Eggshell has a high rate (380 mg/g) of strontium (Sr). Sr has an anabolic effect on the human bone metabolism and strengthens the enamel layer of the teeth.
  • F, Cu and Se which are the other elements found in the eggshell, also have an positive effect on the bone metabolism.
  • the chicken eggshell contain a large number of bioactive molecules.
  • bioactive substances found in eggshell extracts that play important roles are ovotransferrin, ovocleidin-17, ovocleidin-116, osteopontin (OPN), ovalbumin, ovocalyxin-21, ovocalyxin-25, ovocalyxin-32, ovocalyxin- 37, clusterin and lysozyme.
  • OPN which is one of the matrix proteins in the eggshell, is a phosphorylated glycoprotein and is highly found in the bone and kidney. OPN has very important roles in bone modeling and remodeling.
  • Clusterin is also is an other molecule found in the eggshell matrix in 2003 and it is possibly synthesized under stress conditions and acts as a chaperon that plays a role in preventing precipitation and gaining structural stabilization of proteins.
  • GAG Glucosaminoglycans
  • the GAGs are anionic polysaccharides formed by the end-to-end binding of disaccharide molecules formed by hexosamine and uronic acid. The majority of GAGs are bound to core proteins to form proteoglycans.
  • the GAGs obtained from the chicken eggshell are composed of 48% of the hyaluronic acid and 52% of galactosaminoglycans (GAAG).
  • GAAGs are the GAGs haning the most chondroitin sulfate-dermatan sulfate copolymers.
  • Ovoglycan consisting of a dermatan sulfate chain, is a polyanionic GAG.
  • Keratan sulfate one of the GAGs found in the eggshell, plays a role in the nucleation stage of crystal formation. It shows high calcium affinity and regulates crystal growth.
  • Cell differentiation and proliferation factor-1 (transforming growth factor-1 , TGF-1 ), calcitonin and progesterone were also detected in low amounts in the eggshell.
  • Eggshell matrix protein fraction contains potential antimicrobial proteins such as histones and b-defensins. Eggshells also contain significant substances that have a bacteriostatic effect on Gram-negative bacteria, E. Coli D31 and P. Aeruginosa. These antibacterial agents prevent the growth of Gram + bacteria, B. subtilis and S. aureus. This effect is due to lysozyme in the cuticle and protein extracts of the outer eggshell. Lysozyme is an enzyme with a length of 129 amino acids, 14.4 kDa that breaks down bacterial cell walls.
  • lysozyme In addition to its antimicrobial effect, lysozyme also plays an important role during eggshell formation, since it determines the morphology of calcite crystals in the CaC03 structure.
  • the organic matrix of the egg white and eggshell also contains large amount of the lysozyme.
  • lysozyme can be used in oral care products such as toothpaste and mouthwash, to protect against bacteria that cause periodontitis and to protect against oral mucosal infections. Oral and topical application of lysozyme has been found to be effective in protection from herpes simplex virus and against HIV.
  • P. Aureginosa, B. Cereus, and S. Aureus are strongly inhibited when 100 pg/mL of soluble eggshell matrix protein is present in the environment.
  • E. coli and S. Enteritidis are weakly inhibited after treatment for up to 4 hours. These proteins show their effects by breaking down the bacterial cell membrane.
  • transferrins in the eggshell There are also transferrins in the eggshell.
  • ovotransferrin is antibacterial because it binds iron in the medium at concentrations of 1 mg/ml or higher.
  • Ovotransferrin which is located close to the pores in the eggshell, shows its antibacterial effect its location.
  • Ovocalyxin-32 is another antibacterial agent found in the cuticle and outer layers of the eggshell. It inhibits the proliferation of B. subtilisin and also has carboxypeptidase inhibitory activity.
  • Ovocalyxin-36 is also another protein found in the eggshell matrix. This protein has similarities with lipopolysaccharide-binding proteins, which increase bacterial membrane permeability, and with members of the PLUNC protein family, which serve as a defense in the eggshell.
  • Potential antimicrobial proteins such as histones and chicken beta-defensins of the acid-soluble eggshell matrix protein fraction were found to be effective against P. Aeruginosa, B. Cereus and S. Aureus.
  • micronized eggshell powder prepared under suitable conditions can support remineralization positively by preventing the development of infection with the bioactive substances it contains, as well as providing the Ca+2 ions necessary for the remineralization of the caries area, with its high CaC03 content.
  • the membranes are composed of 70% of organic materials, 10% of inorganic materials, and 20% of water.
  • the membranes contain 16% of nitrogen, 2% of saccharides, and 1.35-1.40% of lipids.
  • the ratio of neutral lipids to complex lipids is 86:14.
  • 63% is sphingomyelin and 12% is phosphatidylcholine.
  • the membranes consist of a filamentous protein network that is insoluble in water. Membrane proteins in filamentous form provide the membrane with semi-permeable properties.
  • the shell membranes contain a significant amount of cystine, and since 5- hydroxylysine is also present, they contain a significant amount of collagen.
  • the filamentous elements of the inner and outer subshell membranes are mostly composed of Type-I, Type-V and Type-X collagen.
  • Desmosine, isodesmosine, and a non-elastin protein also exist as a cross linker protein in the shell membranes.
  • the egg shell membrane contains 5-10% hyaluronic acid by weight basis.
  • the membrane contains 2-5% w/w (w/w) of hexosamine, 0.3-3.0% (w/w) of chondroitin and 5-30% (w/w) of collagen.
  • the collagen ratio was found to be 35% by wet weight basis, when based on the 4.5% hydroxyproline amino acid content.
  • the most abundant collagen is Type-I collagen; there are also Type-V and Type-X collagens to a lesser extent.
  • Type-X collagen is known as the collagen that controls tissue mineralization. Glucosamine ratio was 5- 10% and chondroitin ratio was determined as 9% by wet weight basis.
  • the eggshell membranes contain high levels of arginine, glutamic acid, methionine, histidine, cystine and proline amino acids. At the same time, hydroxy proline, hydroxylysine and desmosine amino acids are also abundant. Cystine is a sulfur-containing amino acid that is essential for healthy skin, hair, bone and connective tissue. There is plenty of cystine in the structure of the alpha-keratin protein, which forms the nail, hair and skin tissues and is also found in the oral mucosa. Cysteine takes part in the formation of collagen-containing tissues and increases the elasticity of the skin. Cysteine supplementation accelerates the healing of burns and other types of wounds, increases the flexibility of the joints in arthiritis.
  • the eggshell membranes also contain bacteriolytic enzymes such as N-acetyl glucosaminidase. Some components in the membrane reduce the resistance (thermal resistance) of Gram-positive and Gram-negative pathogenic bacteria (S. Enteritis, E. Coli 0157 : H7, L. Monocytogenes and S. Aureus) to high temperatures.
  • the shell membranes also contain acidic GAGs. Of these, dermatan sulfate and chondroitin sulfate are the most important.
  • the membranes also contain sulfated glycoproteins. Glycoproteins include hexosamine, hexose and fucose.
  • ovotransferrin desmosine and isodesmosine
  • lysyl oxidase lysozyme
  • Oral and injectable preparations containing GAGs in the eggshell membrane, chondroitin sulfate, hydrolyzed or natural forms of collagen, sodium hyaluronate, manganese ascorbate chelate and L- malic acid are used in the prevention and treatment of connective tissue and skin diseases.
  • the composition containing these substances contributes positively to wound healing by accelerating the synthesis activity of chondrocytes and is effective in maintaining tissue health.
  • preparations containing collagen and GAG suspensions for topical use are also used. For this reason, the use of eggshell membrane and/or its components in pulp and tissue lesions around the teeth may provide significant benefits.
  • the eggshell membrane also contains the enzyme lysyl oxidase, a copper- containing amine oxidase with the quinocofactor lysine tyrosylquinone (LTQ) in its active site.
  • This enzyme plays important roles in the development and repair of connective tissue. In case of dietary copper deficiency, connective tissue damage occurs in the gingival tissue, as in other regions. For this reason, the presence of eggshell membrane and/or its components in the dental material to be used in oral care products and in the closure of the contact area of endodontically treated teeth may contribute to the repair of the damaged area and maintaining its healthy condition.
  • BSE bovine spongious encephalopathy
  • Eggshell and shell membranes and their products do not contain animal tissue and most importantly genetic material. Since the eggshell membrane is the only biological material that does not contain DNA, its antigenicity is low and it is less likely to cause allergic reactions. Therefore, eggshell powder and eggshell membrane or their products have ideal properties that can be used in the preparation of dental materials. Because that eggshell and shell membranes are easy to obtain and rich in antibacterial proteins, they have a strong potential for use in the field of health.
  • Stmp binds to the demineralized collagen matrix by providing phosphorylation of soluble type i collagen by forming covalent bonds between the phosphate group and hydroxyl or amino groups in alkaline conditions, and allows the collection of acp nanoprecursors at the remineralization site. This event ensures the attachment of phosphate groups to the collagen membrane. Phosphate groups on the phosphorylated type i collagen trap calcium ions, by lowering the surface energy required for the transition to the crystalline phase, making them preferred nucleation centers the resulting mineralization is heterogeneous, and the formed crystal structure is initially octa-calcium phosphate, and this molecule subsequently transforms into the more stable hydroxyapatite.
  • the collagen membrane surface treated with stmp acts as a nucleation center that triggers mineralization by this mechanism, the surface of type i collagen treated with stmp is mineralized.
  • This phenomenon is a strategy that mimics biomimetic remineralization to induce directed growth of apatite crystals phosphate groups of stmp can bind to the surface of collagen fibers at depths of hundreds of micrometers (up to 300 pm) in the caries area.
  • MMPs matrix metalloproteinases
  • MMPs are the enzymes that are activated in the presence of Ca+2 and Mg+2, removing these ions from the environment inhibits their activities. Therefore, STMP can be applied simultaneously to reduce the destruction of the dentin matrix in dental caries and to provide remineralization. As seen in clinical practice, dentin softens and becomes infected, and disperses in an acid environment. In newly formed caries, this demineralization layer is thick. If this layer can be sufficiently remineralized, preservation of the tooth is possible. STMP is not very effective at nontoxic concentrations of 0.5% or 1% as it is not sufficient to bind all of the Ca+2 ions in the environment.
  • the dental varnish After the dental varnish is applied to the tooth, it forms a homogeneous film layer on the tooth surface with the evaporation of the solvent in its content, and when this film layer comes into contact with the saliva, it binds to the area with the help of its resin content.
  • Bioactive substances such as Ca+2, P04-3 HC03-1 ions and potential antimicrobial proteins such as type I, type V and type X collagens, histones and beta-defensins, osteopontin, GAGs found in eggshell powder liberated and precipitate into demineralized pores and fissures on the tooth surface, as a result of contact with saliva.
  • bioactive substances on the tooth surface initiate remineralization at the demineralization site.
  • STMP covalently binds to the NH+3 groups of collagen fibers at a depth of hundreds of micrometers (up to 300 pm), which are exposed in the demineralization area with its phosphate group under alkaline conditions.
  • ions such as calcium, phosphate and carbonate, which are the basic components of hydroxycarbonapatite playing a very important role in the remineralization of the tooth and gaining the remineralization area the natural structure of the tooth..
  • This phenomenon is a strategy that mimics biomimetic remineralization to induce directed growth of apatite crystals. Since this layer formed at first is very thin, it has an amorphous structure. However, it thickens over time and a hydroxycarbonapatite (HCA) layer is formed, which is chemically and structurally very similar to the mineral composition of the tooth. In this way, open dentin tubules are closed and dentin sensitivity healed, contributing to the repair of the damaged area and maintaining its healthy condition.
  • HCA hydroxycarbonapatite
  • the invention is related to a florine-free dental varnish, which is applied on the tooth surface to prevent development and progress of dental caries in demineralised enamel, on the other hand contributing alleviaton of gingival inflammations and regeneration of gingival lesions, not stimulating gag and split reflex with its aroma, hardening soon after appliying to the tooth surface, not causing allergic reactions and systemic or local toxications, not containing florine, containing micronized eggshell powder and tri-sodium tri-metaphosphate adsorbed eggshell membrane.
  • the eggshells and membranes of the fresh eggs, whose contents are emptied, are separated by an appropriate method and dried separately under 300 mbar vacuum at 50°C overnight.
  • the membrane material prepared in item 1 is first mixed in a 5% acetic acid solution for 1 hour, and then kept overnight in ether-acetone (v/v) by shaking every 2 hours, in order to remove remaining calcium salts and oil and oil-soluble residues. After filtration, the membrane pieces are dried in an oven at 50°C overnight.
  • the membrane pieces obtained by the method in Item 2 are treated for 48 hours at 37°C, by shaking every 2 hours in 3200 U/mg pepsin prepared with 1% (w/v) 0.5M acetic acid solution for the removal of proteins other than collagen. At the end of the period, the enzymatic activity is inhibited by adding 0.2 mg/100 ml pepstatin to 100 ml.
  • the membrane pieces washed with distilled water are treated with 0.2 M STMP at a pH of 11.5 at room temperature for 24 hours to bind phosphate groups to the collagen fibers.
  • the filtered membrane pieces are dried in an oven at 50°C overnight and ground into powder. 4. Powdering the eggshell and eggshell membrane particles
  • the eggshell pieces prepared in item 1 and the membrane pieces prepared in item 3 are ground to a micronized powder in a suitable grinder where overheating is prevented.
  • the prepared products are stored in a dry and cool environment until the dental varnish is prepared.
  • Dental varnish is a dental varnish that contains resin that ensures homogeneous spreading on the tooth surface and adhesion of the content to the tooth surface, STMP-adsorbed eggshell membrane and eggshell powder, xylitol as an artificial sweetener and suitable aroma.
  • STMP sodium trimetaphosphate
  • ethyl alcohol, desired flavoring substance, xylitol as artificial sweetener, sodium fluoride (NaF) are optionally added to the high-speed planetary mixer depending on the amount of tooth varnish to be prepared and mixed thoroughly for half an hour.
  • a sufficient amount of resin is added into the mixture and mixed until it completely dissolves.
  • PEG poly ethylene glycol
  • CMC carboxy methyl cellulose
  • Xantan gum are added into the mixture and the mixture is thoroughly mixed in the high-speed planetary mixer.
  • the membrane and shell powder obtained by the preparation methods described in Items 3 and 4 is added to the mixture and mixed thoroughly. The amount of membrane powder is adjusted so that it is at least 2% by weight of the total product.
  • the final pH of the prepared mixture is adjusted to 9 with sodium bicarbonate and homogenization is ensured by mixing in the mixture at very high speed for 1 more hour.

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  • Health & Medical Sciences (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Dental Preparations (AREA)

Abstract

L'invention concerne un vernis dentaire exempt de florine, qui est appliqué sur la surface de la dent pour empêcher le développement et la progression de caries dentaires dans l'émail déminéralisé, et qui contribue par ailleurs à l'atténuation des inflammations gingivales et à la régénération des lésions gingivales, ne stimule pas le réflexe nauséeux et de rejet avec son arôme, durcit rapidement après application sur la surface de la dent, ne provoque pas de réactions allergiques et de toxicité systémique ou locale, ne contient pas de florine, et contient une poudre de coquille d'oeuf micronisée et une membrane de coquille d'oeuf adsorbée par trimétaphosphate de trisodium.
PCT/TR2022/050250 2021-04-08 2022-03-21 Coquille d'oeuf et membrane de coquille d'oeuf contenant un vernis dentaire WO2022216256A2 (fr)

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TR2021/006313A TR202106313A2 (tr) 2021-04-08 2021-04-08 Yumurta kabuğu ve kabuk zari i̇çeren di̇ş verni̇ği̇
TR2021/006313 TR2021006313A2 (tr) 2021-04-08 Yumurta kabuğu ve kabuk zari i̇çeren di̇ş verni̇ği̇

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EP4393468A1 (fr) * 2022-12-28 2024-07-03 Septodont ou Septodont SAS ou Specialites Septodont Composition de vernis dentaire anhydre

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JP2007197393A (ja) * 2006-01-30 2007-08-09 Yukio Hasebe 歯磨
WO2014021797A2 (fr) * 2012-07-30 2014-02-06 Melek Akman Matériau de ciment pour renouveler des tissus dentaires endommagés

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4393468A1 (fr) * 2022-12-28 2024-07-03 Septodont ou Septodont SAS ou Specialites Septodont Composition de vernis dentaire anhydre
WO2024141586A1 (fr) * 2022-12-28 2024-07-04 Septodont Ou Septodont Sas Ou Spécialités Septodont Composition de vernis dentaire anhydre

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