WO2015167257A1 - Composition for oral application and method for preparing same - Google Patents

Composition for oral application and method for preparing same Download PDF

Info

Publication number
WO2015167257A1
WO2015167257A1 PCT/KR2015/004343 KR2015004343W WO2015167257A1 WO 2015167257 A1 WO2015167257 A1 WO 2015167257A1 KR 2015004343 W KR2015004343 W KR 2015004343W WO 2015167257 A1 WO2015167257 A1 WO 2015167257A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
oral application
clause
acid
lewis
Prior art date
Application number
PCT/KR2015/004343
Other languages
French (fr)
Korean (ko)
Inventor
황동수
오동엽
안진수
차형준
전상호
주성원
프라자테리스티아에카비안티
Original Assignee
포항공과대학교 산학협력단
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from KR1020150059920A external-priority patent/KR20150124919A/en
Application filed by 포항공과대학교 산학협력단 filed Critical 포항공과대학교 산학협력단
Priority to US15/307,800 priority Critical patent/US20170049669A1/en
Publication of WO2015167257A1 publication Critical patent/WO2015167257A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/26—Iron; Compounds thereof

Definitions

  • composition for oral application and its manufacturing method
  • the present invention relates to a composition for oral application and a method for producing the same, and more particularly, to a composition for oral application comprising a Lewis base and Lewis acid of a specific component and a method for producing the same.
  • Dental tissue is composed of enamel, cement and dentin.
  • the outermost part of the exposed part of the tooth is covered with enamel, and the outer part of the root of the tooth located in the alveolar bone is covered with cement and dentin is enclosed by enamel and cement.
  • microtubules called dental tubles are distributed throughout the dentin.
  • the main causes of ache are known cervical abrasion cervical abfracture due to dental caries, windworms (periodontal disease, periodontitis, periodon titis) and incorrect brushing.
  • Tooth decay occurs mainly on the chewing side of the tooth, or on the adjacent side between the tooth and the tooth, which destroys the enamel surrounding the dentin, which exposes the dentin and the dentin tubules, causing the tooth to feel cold.
  • This stratified disease is mainly associated with age groups where enamel is not sufficiently strengthened in infancy and adolescence.
  • the periodontal disease known as gum disease, is caused by damage to the periodontal ligaments that connect teeth and alveolar bones. Exposed, the teeth feel ache.
  • the periodontal disease is mainly seen in adults after the 30s, most of which is insensitive to the reality.
  • Cervical abrasion (cervical abfracture) is mainly caused by poor brushing, and cervical abrasion is the most common cause of cervical abrasion.
  • Enamel or cement which is the outer membrane surrounding the dentin in the cervical region, is very thin. If there is a habit of brushing from side to side with strong force while brushing or enjoying hard food, the enamel or cement of the cervical region may be affected by external stimulation. Damaged, exposed dentin and dentinal tubules, the teeth feel ache symptoms ⁇
  • Hydrodynamic theory is widely accepted that as the flow of dentin flows, external stimuli are transferred to the pulp, causing pain.
  • the pulp nerve desensitization is a treatment to artificially increase the content of potassium ions by controlling the neurotransmission by the proper ratio of sodium ions and potassium ions, thereby preventing the nerves from feeling pain.
  • Topical fluorine coating, oxalic acid-based coating, resin coating, and the like are mainly used as a treatment for applying exposed ivory tubules with other materials to prevent exposure to external stimuli.
  • the ivory capillary sealing method is frequently performed in the dentistry, and thus, studies on various coating materials having excellent durability, human safety, and ease of application are needed.
  • the present invention is to provide a composition for oral application excellent in durability, human safety, and ease of application and a method for producing the same.
  • the present invention is selected from the group comprising tannic acid (galnic acid) and gallic acid (gallic acid)
  • At least one Lewis base At least one Lewis base; And iron (II) ions, iron (III) ions, strontium (III) ions, calcium (II) ions, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ) It provides a composition for oral application, comprising at least one Lewis acid selected from the group consisting of calcium oxide (CaO), calcium hydroxide (Ca (OH) 2 ), silicon (Si), and silica (Si0 2 ). .
  • Lewis acid selected from the group consisting of calcium oxide (CaO), calcium hydroxide (Ca (OH) 2 ), silicon (Si), and silica (Si0 2 ).
  • At least some of the Lewis base and Lewis acid may be present in the form of a complex in which the Lewis base is coordinated with the Lewis acid.
  • the complex compound may include one or more selected from the group consisting of a coordination complex, a 4 coordination complex, and a 6 coordination complex.
  • composition may comprise the Lewis base and the Lewis acid in a concentration of about 0.01 mg / ml to about lmg / ml, respectively, in the composition.
  • the Lewis base and the Lewis acid may be included in a molar ratio of 0.5: 1 to 10: 1.
  • the composition may have a pH value in the range of about 3 to about 8.
  • the composition may further comprise silica particles, it may be preferable that the silica particles have a number average particle diameter of about 0.05;
  • the above-described composition may have various forms of formulation such as solution, paste, aerosol, or resin.
  • the present invention is one or more Lewis base selected from the group comprising tannic acid (galnic acid) and gallic acid (gallic acid); And iron ( ⁇ ) ions, iron (III) ions, strontium (III) ions, calcium ( ⁇ ) ions, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 )
  • the Lewis base and the Lewis acid may be reacted in a molar ratio of about 0.5: 1 to about 10: 1.
  • the reaction may be preferably performed at a pH of about 3 to about 8, and may be preferably performed under a temperature range of 4 to 60 ° C and a pressure range of about 0.1 to about 5 atm.
  • the complex of the Lewis base and the Lewis acid may further comprise the step of coating the silica particles.
  • composition for oral application of the present invention is excellent in durability, human safety, and ease of application, and can be effectively applied inside the oral cavity, which can alleviate or treat the symptom of the syrup, and, when the syrup is applied before the symptom appears, This symptom can be prevented.
  • 1 is an SEM image observed at different magnifications for various surfaces of a dental specimen.
  • Figure 3 is an SEM image observed at different magnification for the surface of the dental specimen treated with the composition according to an embodiment of the present invention.
  • Figure 4 is an SEM image observed by varying the magnification for various cross-sections of the dental specimen treated with the composition according to an embodiment of the present invention.
  • Figure 5 is an SEM image observed before and after the treatment of the composition according to an embodiment of the tooth specimen on the surface of the dental specimen.
  • FIG. 6 is an SEM image of a composition including ordinary silica particles and silica particles according to an embodiment of the present invention.
  • Figure 7 shows the EDX spectrum on the surface of the tooth specimen after treatment with the composition according to an embodiment of the present invention.
  • FIG. 9 is an SEM image of the front and cross sections of a dental specimen before and after treatment of the composition according to an embodiment of the present invention.
  • 10 is an SEM image of the front and the cross-section of the tooth specimen before and after the treatment of the composition according to an embodiment of the present invention.
  • Figure 11 is an SEM image of the front and cross-section of the tooth specimen before and after the treatment of the composition according to an embodiment of the present invention.
  • Oral application composition of the present invention comprises at least one Lewis base selected from the group comprising tannic acid (tannic acid) and gallic acid (gallic acid); And iron (II) ions, iron (III) ions, strontium (III) ions, calcium (II) silver, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ), at least one Lewis acid selected from the group consisting of calcium oxide (CaO), calcium hydroxide (Ca (OH) 2 ), silicon (Si), and silica (Si0 2 ).
  • Lewis base selected from the group comprising tannic acid (tannic acid) and gallic acid (gallic acid);
  • the method for preparing a composition for oral application of the present invention comprises at least one Lewis base selected from the group comprising tannic acid and gallic acid; And iron (II) ions, iron (III) ions, strontium ( ⁇ ) ions, calcium (II) ions, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ) Reacting at least one Lewis Sanol selected from the group comprising calcium oxide (CaO), calcium hydroxide (Ca (OH) 2 ), silicon (Si), and silica (Si0 2 ).
  • Lewis base selected from the group comprising tannic acid and gallic acid
  • each layer or element when each layer or element is referred to as being formed “on” or “on” of each layer or element, it means that each layer or element is formed directly on each layer or element, or It is meant that a layer or element can additionally be formed between each layer, on the object, the substrate.
  • Oral application composition comprises at least one Lewis base selected from the group comprising tannic acid (tannic acid) and gallic acid (gallic acid); And iron (II) ions, iron (III) ions, strontium (III) ions, calcium (II) silver, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ), at least one Lewis acid selected from the group consisting of calcium oxide (CaO), calcium hydroxide (Ca (OH) 2 ), silicon (Si), and silica (Si0 2 ).
  • Lewis base selected from the group comprising tannic acid (tannic acid) and gallic acid (gallic acid);
  • at least one Lewis acid selected from the
  • At least some of the above-described Lewis base and Lewis acid may be present in the form of a complex in which the Lewis base is coordinated with the Lewis acid.
  • fluorine or resin is applied locally to prevent the exposure of dentin tubules.
  • polydopamine is used to remove damaged enamel layer. Research has been conducted on how to promote regeneration.
  • Tannin acid is a kind of natural polyphenol synthesized in various plants and may have a structure of the following formula.
  • the molecular structure of tannic acid is not limited thereto, and may exist in the form of various polymers having various functional groups.
  • Gallic acid is also a non-flavonoid family of natural antioxidants and can be structurally represented as 3,4,5-trihydroxybenzoic acid, but in its natural state it is present in the form of various forms of polymers or polyphenols. can do. Tannic acid and gallic acid, as can be seen in the structure described above,
  • the galloyl group present in tannic acid or gallic acid can act as a Lewis base, due to the non-covalent electron pairs abundant in the hydroxyl group or the carboxy group, and can be used as iron (II) ions, iron (III) ions, Strontium (III) ions, chalc ( ⁇ ) ions, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ), chame oxide (CaO), calcium hydroxide (Ca (OH 2 ), silicon (Si), and silica (Si0 2 ) to form coordination bonds with various forms of Lewis acids to form stable complexes such as octahedral structures.
  • each galloyl group can form a cross link around a different Lewis acid, it forms a rigid bond similar to that of a polymer resin, and thus can be easily bonded to the tooth surface. .
  • the complex compound coordinated with Lewis base to Lewis acid which may be present in the composition may be Since a coating layer can be formed on the surface and the dentinal tubule can be effectively blocked, the virus can effectively prevent or alleviate the symptoms.
  • the above-described complex is about 10 nm to about 1 thick on the surface of the damaged tooth
  • the coating layer may be formed to a thickness of about 20 nm to about 500 nm, thereby effectively sealing the ivory tubule having a diameter of about 0.5 to about 2 ⁇ .
  • the saliva and calcium and phosphorus components contained in the tooth surface can be easily deposited on the complex coating layer due to the many functional groups present inside the tannic acid or gallic acid molecules, which causes the hydroxyapatite layer to be described above. It can be easily formed on the coating layer.
  • Tannic acid or gallic acid is present in a large amount in natural foods such as grapes, persimmons, chestnuts, acorns, green tea, and the like, and is a polyphenol material that has been absorbed by the human body for thousands of years.
  • Tannic acid or gallic acid can be easily obtained as a natural product, and industrially, wood can be easily extracted from the remaining bark and the like, so the price is also very excellent.
  • a molecule of tannic acid or gallic acid or a small unit of the above-mentioned complex compound molecules is adsorbed onto the surface of the tooth, followed by other tannic acid or gallic acid molecules, the Lewis acid material described above, or While forming cross linking with the complex molecule, a coating layer is formed on the surface of the tooth.
  • the complex of the Lewis base and the Lewis acid may include one or more selected from the group consisting of a double coordination complex, a fourth coordination complex, and a six coordination complex.
  • the coordination complex (mono-complex) is a Lewis base in Lewis acid as described above.
  • a bi-complex complex means that four hydroxyl groups of the Lewis bases described above are coordinated with Lewis acid to form a ligand.
  • 6 coordination complex tris-complex means that six hydroxyl groups of Lewis bases mentioned above are coordinated with Lewis acid to form a ligand.
  • Lewis (I) ions iron (III) ions, strontium (III) ions, and / or calcium (II) ions are used as Lewis acids, these metal ions may become central metals to form complexes.
  • Silica (Si0 2) may be such a case that is used as a Lewis acid include, these hydroxy-ethoxy group of the Lewis base described above to nano-size particles (particle nan o) of the material is to form a coordination complex.
  • the nano-size particles described above may have a particle size of about 10 nm to about 1, and such complex compounds are more specifically, for example, in the form of the following structural formula. ⁇
  • Me is a Lewis acid in which iron (II) ions, iron (III) ions, strontium (III) ions, and / or calcium (II) ions are used.
  • the complex used in the present invention is not necessarily limited to the above-described structural formula, and may be composed of complex compounds having various structures and coordination numbers, depending on the type of Lewis acid and Lewis base used.
  • Each galloyl group in the above structural formula may be in the form of a chelate belonging to the same tannic acid or gallic acid molecule, or may belong to another tannic acid or gallic acid molecule and form a crosslink with a neighboring complex compound.
  • the complex compounds may be common to each other depending on external conditions such as temperature, ⁇ , etc., in the state of the composition and the state applied to the oral cavity.
  • the composition may include the Lewis base and the Lewis acid in a concentration of about img / ml to about lmg / ml, respectively.
  • concentration of the Lewis base and the Lewis acid is lower than the above range, the amount of the complex compound to be produced may not be divided, and the coating layer may not be formed.
  • the present invention is not necessarily limited thereto, and the concentration of the Lewis base and the Lewis acid may vary depending on the application site and the application conditions when the vaccine is applied for treatment and prevention.
  • the composition may preferably comprise the Lewis base and the Lewis acid in a molar ratio of about 0.5: 1 to about 10: 1. If the molar ratio of the Lewis base and the Lewis acid is lower than the above range, the amount of Lewis base may not be sufficient in amount, and thus, a large amount of unshared electron pairs may not be provided to the Lewis acid, and crosslinking may not be formed in a sufficient amount. When the molar ratio of the Lewis base and the Lewis acid is higher than the above range, the amount of Lewis acid, which is the center of the complex compound, may be less, and crosslinking may not be sufficiently formed.
  • the composition may preferably have a pH in the range of about 3 to about 8, more preferably in the range of about 6 to about 7.6.
  • This pH range is also a range having an acidity similar to the environment in the oral cavity, but the complex compound described above in the pH range is 4 to 10 or 4 coordination.
  • ⁇ When ⁇ is lower than the above range, due to the high hydrogen ion concentration, the hydroxyl group of the galloyl group is present in the central Lewis acid of the complex. Failure to provide ligands can lead to problems in which crosslinking cannot be effectively formed.
  • ⁇ is higher than the above range, it is likely that the hydroxide ions will provide the lone pair with the above-mentioned Lewis acid due to the high concentration of hydroxide ions.
  • PBS phosphate buffered saline
  • NaOH sodium hydroxide aqueous solution
  • the composition may further comprise separate silica particles.
  • the silica particles referred to herein are used as Lewis acids of the composition and are further included separately in addition to the nano-sized silica which forms a complex with tannic acid or gallic acid.
  • Silica particles may act as a nucleus for forming a coating layer by a complex compound in the above-described crosslink formation process, and the surface may be coated by the complex compound to fill a loss part of a tooth when a syringe is used for treatment or the like. Can play a role in the body. Silica particles coated on the surface by the above-described complex compound may penetrate into the dentin tubules to block the dentin tubules, and the hydroxyapatite layer described above may be formed to regenerate damaged tooth portions.
  • Such silica particles may preferably have a number average particle diameter of about 0.05 m to about 5.
  • the number average particle diameter of the silica particles is smaller than the above range, the surface coating may not easily occur due to the complex compound. If the number average particle diameter of the silica particles is larger than the above range, the silica particles may not penetrate into the ivory tubule.
  • the present invention is not necessarily limited thereto.
  • the silica particles may be preferably included in about 50% by weight or less based on the total composition.
  • the calculated ⁇ value is in the range of about 3 to about 25, preferably in the range of about 3 to about 15, more preferably in the range of about 3 to about 6, and is difficult to visually identify before and after treatment. Only the color change may be brought or there may be little color change.
  • the AW * value calculated by the following equations (2) and (3) is in the range of about -7 to 20, preferably in the range of about 0 to about 20, more preferably In the range of about 2 to 6, the teeth whitening index is
  • composition is aerosol, which can be applied as a solution such as gargle or coating liquid, paste, spray solution, etc. which can be applied as toothpaste or ointment, or
  • It may have a formulation in the form of a resin that can be used for application.
  • the patient In the case of preparation of the gargle, the patient directly holds the gargle in the mouth for several tens of seconds and then repeats the method of rinsing, thereby easily treating and preventing the syringe.
  • Treatment is possible through curing.
  • the composition described above as one component of the toothpaste It is possible to treat and prevent symptomatic symptoms by repeating brushing with such toothpaste.
  • a method for producing a composition for oral application at least one Lewis base selected from the group comprising tannic acid (tannic acid) and gallic acid (gallic acid); And iron ( ⁇ ) ions, iron (III) ions, strontium (III) ions, calcium (II) ions, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ) And at least one Lewis acid selected from the group consisting of calcium oxide (CaO), calcium hydroxide (Ca (OH) 2 ), silicon (Si), and silica (Si0 2 ).
  • the reaction method is not particularly limited, and for example, after preparing an aqueous solution of each of Lewis base and Lewis acid, the reaction can be advanced simply by mixing and stirring the mixture.
  • metal ions when metal ions are used as the Lewis acid described above, various metal salts may be used as precursors for generating the metal ions.
  • the Lewis base and the Lewis acid may be preferably reacted by mixing in a molar ratio of 0.5: 1 to 10: 1, and the description of the ratio limitation is as described in the composition.
  • the step of reacting may be preferably performed in a pH range of 3 to 7.5, the reason for limiting such pH is also as described in the composition.
  • the reaction may be performed under a temperature range of 4 to 60 ° C and a pressure range of 0.1 to 5 atm, and more preferably performed under a temperature range of 15 to 40 ° C and a pressure range of 0.1 to 2 atm. And, it may be most preferably performed under a temperature range of 30 to 40 ° C and a pressure range of 0.5 to 1.5 atm, which is a similar environment as the oral cavity, the present invention is not necessarily limited thereto, It is possible to perform without the constraints of the instrument.
  • the silica particles in addition to coating the silica particles with a complex compound that is a product of the reaction It may further comprise a step.
  • the coating method is not particularly limited, and for example, the surface-coated silica particles can be obtained only by immersing the aqueous solution of each of the Lewis base and Lewis acid so as to evenly disperse the above-described silica particles in a mixed composition.
  • the ivory tubule sealing method comprising the step of forming a coating layer by applying the composition for oral application in the oral cavity exposed to the dentin tube can be provided.
  • the method may further include forming a hydroxyapatite layer, which is described above in the description of the composition for oral application.
  • a hydroxyapatite layer which is described above in the description of the composition for oral application.
  • teeth without caries and restorations were prepared. Extracted teeth were stored in l% chloramine T solution until testing. A tooth specimen was prepared by removing the crown of the tooth using a low-speed diamond rob and cutting it to lmm thickness to expose the dentin. The cut surface was mirror polished up to 3000 mesh using sandpaper, and the specimen was washed in the order of acetone, ethanol and distilled water in an ultrasonic cleaner and dried at room temperature.
  • FIG. 1 is an SEM image of various parts of the prepared surface of the dental specimen at different magnifications.
  • FIG 1 it can be seen that the ivory tubules are exposed on the surface of the specimen.
  • Figure 2 shows different magnifications for various cross sections of the prepared dental specimens. The observed SEM image.
  • a composition comprising a complex compound was prepared.
  • Silica particles (Sigma Aldrich) having an average particle diameter of 50 to 100 nm were added to the composition prepared in Example 1.
  • the silica particles on the right side can be seen that a relatively transparent film is formed on the surface thereof, and this film is formed by depositing a tannic acid-iron (III) complex on the surface of the silica particles. It can be interpreted as forming a coating layer.
  • aqueous solution of tannic acid at a concentration of 0.8 mg / ml and an aqueous dispersion of titanium dioxide ( ⁇ 0 2 ) nanoparticles (particle size: 10 nm to 1 ⁇ , manufacturer: Sigma Aldrich) at 0.2 mg / ml were prepared. After mixing 5 ml of each of the aqueous solution and the aqueous dispersion, and then dropping the phosphate buffer solution until the pH is 7 or more, the tannin acid and titanium dioxide nanoparticles A composition comprising a complex compound was prepared.
  • Strontium (Sr (N0 3 ) 2 ) aqueous solution was prepared.
  • a nanoparticle (particle diameter: 10 nm to ffli, manufacturer: Sigma Aldrich) was prepared with an aqueous dispersion. After mixing 5 ml of each of the aqueous solution and the aqueous dispersion, and then dropping the complete phosphate solution until ⁇ was 7 or more, a composition including a complex compound of tannic acid and silica nanoparticles was prepared.
  • aqueous solution of tannin acid at a concentration of 0.8 mg / ml and an aqueous dispersion of iron oxide (Fe 2 O 3 ) nanoparticles (particle size: 10 nm to ⁇ , manufactured by Sigma Aldrich) at a concentration of 0.2 mg / ml were prepared. After mixing 5 ml of each of the aqueous solution and the aqueous dispersion, and then dropping the complete phosphate solution until ⁇ is 7 or more, a composition containing a complex compound of tannic acid and iron oxide nanoparticles was prepared.
  • aqueous solution of tannin acid at a concentration of 0.8 mg / ml and a calcium hydroxide (Ca (OH) 2 ) nanoparticle (particle size: 10 nm to 1 // II1, manufactured by Sigma Aldrich) at 0.2 mg / ml were prepared. After mixing 5 ml of each of the aqueous solution and the aqueous dispersion, and then dropping the phosphate buffer solution until ⁇ is 7 or more, the tannin acid and calcium hydroxide nanoparticles
  • composition comprising a complex compound was prepared. [Example 1-1 and Examples 3-1 to 7-1]
  • Example 1 The same procedure as in Example 1 and Examples 3 to 7 was performed except that an aqueous solution of gallic acid was used instead of an aqueous solution of tannic acid.
  • the prepared tooth specimen was immersed in the composition of the above Example for about 1 minute, after immersion, taken out and washed with distilled water. Several immersion washes were repeated four times. Observation of the tooth surface
  • salts of calcium chloride (CaCl 2 ), potassium phosphate (potassium phosphate, K 2 HP0 4 ), sodium fluoride (NaF) and sodium chloride (NaCl) were added to the following concentrations, respectively.
  • the tooth composition treated with the composition was immersed, put in a rotary incubator and stored at a rate of 37 ° C, 100 rpm for a week. During storage, artificial saliva was refreshed every 24 hours. After 7 days, the specimens were taken out, washed with distilled water, some of them were collected, and the surface and the cross section thereof were observed by SEM.
  • Example 3 is an SEM image observed on the surface of the dental specimen treated with the composition of Example 1.
  • FIG. 4 is an SEM image of various cross sections of the dental specimen to which the composition of Example 1 is treated.
  • the coating filling is formed on the surface of the specimen, to form a uniform height, in particular, as observed in Figure 2, it can be seen that the uneven irregularities due to tooth damage, etc. disappeared (right Prize).
  • a lump is formed on the surface of the tooth, which is formed of hydroxyapatite by depositing calcium and phosphorus components of artificial saliva on the coating layer of the tannin-iron (III) complex. It can be confirmed that a layer is formed.
  • FIG. 5 is an SEM image of the dentin tubular surface of the dental specimen surface before and after treatment with the composition of Example 1.
  • FIG. 7 shows the EDX spectrum of the surface of the dental specimen after treatment of the composition of Example 1.
  • Hydroxyapatite layerols collected separately, were measured for EDX spectra for comparison with normal dental specimens and their components.
  • Example 8 is produced after the composition treatment of Example 1 and Example 1-1
  • the hydroxyapatite layer has a composition similar to that of regular teeth. You can check it.
  • 9 to 1 are SEM images observed on the front and cross section of the ivory tubule on the surface of the tooth specimen before and after treatment with the compositions of Examples 1, 3 to 7, 1-1, and 3-1 to 7-1. 9 to 11, when comparing the tooth specimen before the composition treatment and after application, it can be seen that the dentinal tubules on the tooth surface effectively blocked, especially after 7 days of application, a lump is formed on the surface, exposed In addition to the surface of the ivory tubules, the interior of the ivory tubules can be confirmed that the blockage, from which the scab and phosphorus components of artificial saliva are deposited on the coating layer of the complex
  • Example 1 The composition of Example 1 was treated to prepare a dental specimen having a hydroxyapatite layer on the coating layer of the tannic acid-iron (III) complex, which had a diameter of about 10 mm and a thickness of about l mm.
  • the tooth specimens were subjected to 100 times brushing with a load of 150 g using equipment in accordance with ISO 11609.
  • the surface of the specimen was subjected to 100 times brushing with a load of 150 g using equipment in accordance with ISO 11609. The surface of the specimen
  • the color change is not severe in the range of about 3 to about 25 in all embodiments, and in particular, in Examples 4 to 6, the color index ⁇ value is in the range of about 3 to about 6 Because of the location, it can be seen that the color change is not so severe that it is difficult for the naked eye to easily identify the color change.
  • the AW * value too, in all the ranges of about -20 to about 20, it can be seen that the color change is not severe, especially in the case of Examples 3 to 6 W * value to have a positive value It can be seen that the tooth whitening effect can also be expected by applying the composition of the present invention.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Cosmetics (AREA)

Abstract

The present invention relates to a composition for oral application and a method for preparing the same and, more specifically, to a composition for oral application, containing a complex compound of a particular Lewis base and a particular Lewis acid, and to a method for preparing the same. The composition for oral application of the present invention has excellent durability, safety to the human body, and coatability, and thus can effectively treat tooth sensitivity symptoms, and can prevent tooth sensitivity symptoms when being applied prior to the tooth sensitivity symptoms.

Description

【명세서】  【Specification】
【발명의 명칭】  [Name of invention]
구강 도포용 조성물 및 그 제조 방법 【기술분야】  Composition for oral application and its manufacturing method
본 발명은 구강 도포용 조성물과 그 제조 방법에 관한 것으로, 보다 상세하게는, 특정 성분의 루이스 염기 및 루이스 산을 포함하는 구강 도포용 조성물과 그 제조 방법에 관한 것이다.  The present invention relates to a composition for oral application and a method for producing the same, and more particularly, to a composition for oral application comprising a Lewis base and Lewis acid of a specific component and a method for producing the same.
본 출원은 , 2014년 4월 29일자 대한민국 특허 출원 10-2014-0051815호 및 2015년 4월 28일자 대한민국 특허 출원 10-2015-0059920호에 기초한 우선권의 이익을 주장하며， 해당 대한민국 특허 출원의 문헌에 개시된 모든 내용은 본 명세서의 일부로서 포함된다.  This application claims the benefit of priority based on Republic of Korea Patent Application No. 10-2014-0051815 dated April 29, 2014 and Republic of Korea Patent Application No. 10-2015-0059920 dated April 28, 2015, All content disclosed in is included as part of this specification.
【배경기술】 Background Art
치아 조직은 에나멜질 (enamel), 시멘트질 (cement) 및 상아질 (dentin)로 구성되어 있다. 치아 중 노출되어 있는 부분의 가장 바깥쪽은 에나멜질로 덮여 있고, 치조골 내에 위치하는 치아 뿌리 부분의 바깥쪽은 시멘트질로 덮여 있으며, 에나멜질과 시멘트질로 둘러싸인 내부에 상아질이 존재한다. 상아질에는 상아세관 (dental tubles)이라는 미세한 관이 상아질 전체에 걸쳐 분포하고 있다.  Dental tissue is composed of enamel, cement and dentin. The outermost part of the exposed part of the tooth is covered with enamel, and the outer part of the root of the tooth located in the alveolar bone is covered with cement and dentin is enclosed by enamel and cement. In the dentin, microtubules called dental tubles are distributed throughout the dentin.
시린이 (상아질 지각과민증, dentin hypersensitivity)는 열 (thermal),  Sirin (dentin hypersensitivity, dentin hypersensitivity) is thermal,
기화 (evaporative), 접촉 (tactile), 삼투압 (osmotic), 화학적 (chemical) 자극 등의 외부 자극으로 발생하는 짧고 강한 통증을 의미한다. It refers to a short and strong pain caused by external stimuli such as evaporative, tactile, osmotic, and chemical stimuli.
시린이를 일으키게 되는 주 원인은 층치 (dental caries), 풍치 (잇몸질환, 치주염, periodon titis) 및 잘못된 칫솔질 등으로 인한 치경부 마모증 (cervical abrasion cervical abfracture) 등인 것으로 알려져 있다ᅳ  The main causes of ache are known cervical abrasion cervical abfracture due to dental caries, windworms (periodontal disease, periodontitis, periodon titis) and incorrect brushing.
충치는 치아의 씹는 면이나, 치아와 치아 사이의 인접 면에서 주로 발생하며, 상아질을 둘러싸는 에나멜질을 파괴하는데， 이로 인해 상아질과 상아세관이 노출되어 치아가 시린 증상을 느끼게 된다. 이러한 층치 질환은 유아기에서 청소년기에 에나멜질이 층분히 강화되지 못한 연령대에 주로  Tooth decay occurs mainly on the chewing side of the tooth, or on the adjacent side between the tooth and the tooth, which destroys the enamel surrounding the dentin, which exposes the dentin and the dentin tubules, causing the tooth to feel cold. This stratified disease is mainly associated with age groups where enamel is not sufficiently strengthened in infancy and adolescence.
발생하게 된다. 잇몸질환으로 알려진 풍치 (치주염)는 치아와 치조골을 서로 이어주는 치주 인대가 손상되면서 발생하는데, 이 치주 인대의 손상과 동시에 치아 뿌리 부분을 둘러싸고 있던 시멘트질이 손상되면서, 치아 뿌리부분의 상아질과 상아세관이 노출되어, 치아가 시린 증상을 느끼게 된다. 이러한 치주질환은 주로 30대 이후의 성인에서 많이 나타나는데, 대부분이 이 질환에 무감각한 것이 현실이다. Will occur. The periodontal disease, known as gum disease, is caused by damage to the periodontal ligaments that connect teeth and alveolar bones. Exposed, the teeth feel ache. The periodontal disease is mainly seen in adults after the 30s, most of which is insensitive to the reality.
치경부 마모증 (cervical abrasion, cervical abfracture)은 주로 바르지 못한 칫솔질에 의해 발생하는데, 시린이 증상을 호소하는 환자 중 치경부 마모증으로 인한 경우가 가장 많다. 치경부에서 상아질을 둘러싸고 있는 외투막인 에나멜질 또는 시멘트질의 두께는 매우 얇은데, 칫솔질을 하면서 센 힘으로 좌우로 닦거나, 딱딱한 음식을 즐기는 습관이 있는 경우, 외부 자극에 의해 치경부 부위의 에나멜질 또는 시멘트질이 손상되면서， 상아질과 상아세관이 노출되어, 치아가 시린 증상을 느끼게 된다ᅳ  Cervical abrasion (cervical abfracture) is mainly caused by poor brushing, and cervical abrasion is the most common cause of cervical abrasion. Enamel or cement, which is the outer membrane surrounding the dentin in the cervical region, is very thin.If there is a habit of brushing from side to side with strong force while brushing or enjoying hard food, the enamel or cement of the cervical region may be affected by external stimulation. Damaged, exposed dentin and dentinal tubules, the teeth feel ache symptoms ᅳ
상기와 같은 시린이 증상에 대해, 그 통증 발생 및 전달에 대한 메커니즘은 아직 명확히 밝혀지지 않았으나, 상아질을 둘러싸는 에나멜질이나 시멘트질이 손상되면서 , 상아질과 상아세관이 노출되어, 상아세관 (dentinal tubule) 내  For such symptomatic symptoms, the mechanisms for pain generation and delivery are not yet clear, but the dentin and the enamel tubules are exposed as the enamel or cementum surrounding the dentin is compromised, leading to dentin tubules. of mine
상아질액의 유동이 생기면서 외부의 자극이 치수까지 전달되어 통증을 느끼게 된다는 수력학적 이론 (hydrodynamic theory)이 널리 받아들여지고 있다. Hydrodynamic theory is widely accepted that as the flow of dentin flows, external stimuli are transferred to the pulp, causing pain.
그러한 이유로, 상기와 같은 시린이 증상을 치료하기 위해서는 주로 상아세관 밀봉법과 치수 신경 탈 감작법이 주로 적용된다. 치수 신경 탈 감작법은 신경 전달이 나트륨 이온과 칼륨 이온의 적정 비율에 의해 조절되는 점을 이용하여 칼륨 이온의 함량을 인위적으로 높여 줌으로써 신경이 시린 통증을 느끼지 못하게 하는 치료법이며, 상아세관 밀봉법은 노출된 상아세관을 다른 재료 등으로 도포하여 외부 자극에의 노출을 막는 치료법으로, 국소 불소 도포법， 옥살산계 물질 도포법, 레진 도포법 등이 주로 이용된다.  For this reason, the dentinal tubular sealing method and the pulp nerve desensitization method are mainly applied to treat such symptom. The pulp nerve desensitization is a treatment to artificially increase the content of potassium ions by controlling the neurotransmission by the proper ratio of sodium ions and potassium ions, thereby preventing the nerves from feeling pain. Topical fluorine coating, oxalic acid-based coating, resin coating, and the like are mainly used as a treatment for applying exposed ivory tubules with other materials to prevent exposure to external stimuli.
두 방법 중, 상아세관 밀봉법이 치과 등에서 많이 시술되기 때문에, 우수한 내구성, 인체 안전성, 및 도포 용이성 등을 갖는 다양한 도포 물질에 대한 연구가 필요한 실정이다.  Among the two methods, the ivory capillary sealing method is frequently performed in the dentistry, and thus, studies on various coating materials having excellent durability, human safety, and ease of application are needed.
【발명의 내용】 [Content of invention]
【해결하려는 과제】 본 발명은 내구성, 인체 안전성, 및 도포 용이성이 우수한 구강 도포용 조성물과 그의 제조 방법을 제공하고자 한다. [Problem to solve] The present invention is to provide a composition for oral application excellent in durability, human safety, and ease of application and a method for producing the same.
【과제의 해결 수단】 [Measures of problem]
본 발명은 탄닌산 (tannic acid) 및 갈산 (gallic acid)을 포함하는 군에서 선택된 The present invention is selected from the group comprising tannic acid (galnic acid) and gallic acid (gallic acid)
1종 이상의 루이스 염기; 및 철 (II) 이온, 철 (III) 이온, 스트론튬 (III) 이온, 칼슘 (II) 이온， 이산화티타늄 (Ti02), 산화 철 (Fe203), 수산화 철 (Fe(OH)2), 산화 칼슘 (CaO), 수산화 칼슘 (Ca(OH)2), 실리콘 (Si), 및 실리카 (Si02)를 포함하는 군에서 선택된 1종 이상의 루이스 산을 포함하는, 구강 도포용 조성물을 제공한다. At least one Lewis base; And iron (II) ions, iron (III) ions, strontium (III) ions, calcium (II) ions, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ) It provides a composition for oral application, comprising at least one Lewis acid selected from the group consisting of calcium oxide (CaO), calcium hydroxide (Ca (OH) 2 ), silicon (Si), and silica (Si0 2 ). .
상기 상기 루이스 염기 및 루이스 산 중 적어도 일부는 루이스 산에 루이스 염기가 배위된 착화합물 형태로 존재하는 것이 바람직할 수 있다.  At least some of the Lewis base and Lewis acid may be present in the form of a complex in which the Lewis base is coordinated with the Lewis acid.
상기 착화합물은 2배위 착화합물， 4배위 착화합물, 및 6배위 착화합물로 이루어진 군에서 선택된 1종 이상을 포함하는 것일 수 있다.  The complex compound may include one or more selected from the group consisting of a coordination complex, a 4 coordination complex, and a 6 coordination complex.
또한, 상기 조성물은 상기 루이스 염기 및 상기 루이스 산을 조성물 내에 각각 약 0.01mg/ml 내지 약 lmg/ml의 농도로 포함할 수 있다.  In addition, the composition may comprise the Lewis base and the Lewis acid in a concentration of about 0.01 mg / ml to about lmg / ml, respectively, in the composition.
그리고, 상기 루이스 염기 및 루이스 산을 0.5: 1 내지 10:1의 몰 비율로 포함할 수도 있다.  In addition, the Lewis base and the Lewis acid may be included in a molar ratio of 0.5: 1 to 10: 1.
일 예에 따르면, 상기 조성물은 pH 값이 약 3 내지 약 8 범위일 수 있다. 또한, 상기 조성물은 실리카 입자를 더 포함할 수도 있으며, 상기 실리카 입자는, 수평균 입경이 약 0.05；圆 내지 약 5 인 것이 바람직할 수 있다.  According to one embodiment, the composition may have a pH value in the range of about 3 to about 8. In addition, the composition may further comprise silica particles, it may be preferable that the silica particles have a number average particle diameter of about 0.05;
상술한 조성물은 용액, 페이스트， 에어로졸, 또는 레진 등 다양한 형태의 제형을 가질 수 있다. 또한, 본 발명은 탄닌산 (tannic acid) 및 갈산 (gallic acid)을 포함하는 군에서 선택된 1종 이상의 루이스 염기; 및 철 (Π) 이온, 철 (III) 이온, 스트론튬 (III) 이온, 칼슘 (Π) 이온, 이산화티타늄 (Ti02), 산화 철 (Fe203), 수산화 철 (Fe(OH)2), 산화 칼슘 (CaO), 수산화 칼슘 (Ca(OH)2), 실리콘 (Si), 및 실리카 (Si02)를 포함하는 군에서 선택된 1종 이상의 루이스 산;을 반웅시키는 단계를 포함하는 구강 도포용 조성물의 제조 방법을 제공한다. The above-described composition may have various forms of formulation such as solution, paste, aerosol, or resin. In addition, the present invention is one or more Lewis base selected from the group comprising tannic acid (galnic acid) and gallic acid (gallic acid); And iron (Π) ions, iron (III) ions, strontium (III) ions, calcium (Π) ions, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ) At least one Lewis acid selected from the group consisting of calcium oxide (CaO), calcium hydroxide (Ca (OH) 2 ), silicon (Si), and silica (Si0 2 ); Provided are methods for preparing the composition.
그리고, 상기 제조 방법은 상기 루이스 염기 및 상기 루이스 산의 착화합물을 형성하는 단계를 포함할 수 있다. And, the preparation method of the Lewis base and the Lewis acid Forming a complex compound.
위 제조 방법에서는 상기 루이스 염기 및 루이스 산을 약 0.5:1 내지 약 10:1의 몰 비율로 반응시킬 수 있다.  In the above preparation method, the Lewis base and the Lewis acid may be reacted in a molar ratio of about 0.5: 1 to about 10: 1.
상기 반웅시키는 단계는 pH가 약 3 내지 약 8 범위에서 수행되는 것이 바람직할 수 있으며 , 4 내지 60°C의 온도 범위 및 약 0.1 내지 약 5atm의 압력 범위 하에서 수행되는 것이 바람직할 수 있다. The reaction may be preferably performed at a pH of about 3 to about 8, and may be preferably performed under a temperature range of 4 to 60 ° C and a pressure range of about 0.1 to about 5 atm.
일 예에 따르면 상기 루이스 염기 및 상기 루이스 산의 착화합물로, 실리카 입자를 코팅하는 단계를 더 포함할 수도 있다. 【발명의 효과】  According to one example, with the complex of the Lewis base and the Lewis acid, it may further comprise the step of coating the silica particles. 【Effects of the Invention】
본 발명의 구강 도포용 조성물은 내구성, 인체 안전성, 및 도포 용이성이 우수하여, 효과적으로 구강 내부에 도포되어, 시린이 증상올 완화시키거나 치료할 수 있으며, 또한, 시린이 증상이 나타나기 전에 적용 시， 시린이 증상을 예방할 수 있다.  The composition for oral application of the present invention is excellent in durability, human safety, and ease of application, and can be effectively applied inside the oral cavity, which can alleviate or treat the symptom of the syrup, and, when the syrup is applied before the symptom appears, This symptom can be prevented.
또한, 본 발명의 제조 방법에 따르면 상기 구강 도포용 조성물을 쉽게 제조할 수 있다,  In addition, according to the production method of the present invention can easily prepare the composition for oral application,
【도면의 간단한 설명】 [Brief Description of Drawings]
도 1은 치아 시편의 다양한 표면에 대해 배율을 달리하여 관찰한 SEM 이미지이다.  1 is an SEM image observed at different magnifications for various surfaces of a dental specimen.
도 2는 치아 시편의 다양한 단면에 대해 배율을 달리하여 관찰한 SEM 이미지이다.  2 is an SEM image observed at different magnifications for various cross sections of a dental specimen.
도 3은 본 발명의 일 실시예에 따른 조성물이 처리된 치아 시편 표면에 대해 배율을 달리하여 관찰한 SEM 이미지이다.  Figure 3 is an SEM image observed at different magnification for the surface of the dental specimen treated with the composition according to an embodiment of the present invention.
도 4는 본 발명의 일 실시예에 따른 조성물이 처리된 치아 시편의 다양한 단면에 대해 배율을 달리하여 관찰한 SEM 이미지이다.  Figure 4 is an SEM image observed by varying the magnification for various cross-sections of the dental specimen treated with the composition according to an embodiment of the present invention.
도 5는 본 발명의 일 실시예에 따른 조성물 처리 전 후, 치아 시편 표면의 상아세관 대해 관찰한 SEM 이미지이다.  Figure 5 is an SEM image observed before and after the treatment of the composition according to an embodiment of the tooth specimen on the surface of the dental specimen.
도 6은 일반 실리카 입자 및 본 발명의 일 실시예에 따른 실리카 입자를 포함하는 조성물을 관찰한 SEM 이미지이다. 도 7은 본 발명의 일 실시예에 따른 조성물 처리 후, 치아 시편 표면에 대한 EDX 스펙트럼을 나타낸 것이다. 6 is an SEM image of a composition including ordinary silica particles and silica particles according to an embodiment of the present invention. Figure 7 shows the EDX spectrum on the surface of the tooth specimen after treatment with the composition according to an embodiment of the present invention.
도 8은 본 발명의 일 실시예에 따른 조성물 처리 후,  8 is after the composition treatment according to an embodiment of the present invention,
하이드록시아파타이트 층을 수집하여, 이에 대한 EDX 스펙트럼을 나타낸 것이다ᅳ 도 9는 본 발명의 일 실시예에 따른 조성물의 처리 전 후, 치아 시편의 정면 및 단면에 대한 SEM 이미지이다. A layer of hydroxyapatite was collected and shows the EDX spectrum thereof. FIG. 9 is an SEM image of the front and cross sections of a dental specimen before and after treatment of the composition according to an embodiment of the present invention.
도 10은 본 발명의 일 실시예에 따른 조성물의 처리 전 후， 치아 시편의 정면 및 단면에 대한 SEM 이미지이다.  10 is an SEM image of the front and the cross-section of the tooth specimen before and after the treatment of the composition according to an embodiment of the present invention.
도 11은 본 발명의 일 실시예에 따론 조성물의 처리 전 후， 치아 시편의 정면 및 단면에 대한 SEM 이미지이다.  Figure 11 is an SEM image of the front and cross-section of the tooth specimen before and after the treatment of the composition according to an embodiment of the present invention.
도 12는 본 발명의 일 실시예에 따른 조성물이 처리된 치아 시편에 대해 잇솔질을 완료한 후 치아 시편의 표면을 관찰한 SEM 이미지이다.  12 is an SEM image of the surface of the tooth specimen after brushing the tooth specimen treated with the composition according to an embodiment of the present invention.
【발명을 실시하기 위한 구체적인 내용】 [Specific contents to carry out invention]
본 발명의 구강 도포용 조성물은 탄닌산 (tannic acid) 및 갈산 (gallic acid)을 포함하는 군에서 선택된 1종 이상의 루이스 염기; 및 철 (II) 이온, 철 (III) 이온， 스트론톱 (III) 이온, 칼슘 (II) 이은, 이산화티타늄 (Ti02), 산화 철 (Fe203), 수산화 철 (Fe(OH)2), 산화 칼슘 (CaO), 수산화 칼슘 (Ca(OH)2), 실리콘 (Si), 및 실리카 (Si02)를 포함하는 군에서 선택된 1종 이상의 루이스 산을 포함한다. Oral application composition of the present invention comprises at least one Lewis base selected from the group comprising tannic acid (tannic acid) and gallic acid (gallic acid); And iron (II) ions, iron (III) ions, strontium (III) ions, calcium (II) silver, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ), at least one Lewis acid selected from the group consisting of calcium oxide (CaO), calcium hydroxide (Ca (OH) 2 ), silicon (Si), and silica (Si0 2 ).
또한， 본 발명의 구강 도포용 조성물의 제조 방법은 탄닌산 (tannic acid) 및 갈산 (gallic acid)을 포함하는 군에서 선택된 1종 이상의 루이스 염기; 및 철 (II) 이온， 철 (III) 이온, 스트론튬 (ΠΙ) 이온, 칼슘 (II) 이온， 이산화티타늄 (Ti02), 산화 철 (Fe203), 수산화 철 (Fe(OH)2), 산화 칼슘 (CaO), 수산화 칼슘 (Ca(OH)2), 실리콘 (Si), 및 실리카 (Si02)를 포함하는 군에서 선택된 1종 이상의 루이스 산올 반웅시키는 단계를 포함한다. 또한, 본 명세서에서 사용되는 용어는 단지 예시적인 실시예들을 설명하기 위해 사용된 것으로， 본 발명을 한정하려는 의도는 아니다. 단수의 표현은 문맥상 명백하게 다르게 뜻하지 않는 한, 복수의 표현을 포함한다. 본 명세서에서， "포함하다 구비하다" 또는 "가지다'' 등의 용어는 실시된 특징, 슷자， 단계, 구성 요소 또는 이들을 조합한 것이 존재함올 지정하려는 것이지, 하나 또는 그 이상의 다른 특징들이나 슷자, 단계, 구성 요소， 또는 이들을 조합한 것들의 존재 또는 부가 가능성을 미리 배제하지 않는 것으로 이해되어야 한다. In addition, the method for preparing a composition for oral application of the present invention comprises at least one Lewis base selected from the group comprising tannic acid and gallic acid; And iron (II) ions, iron (III) ions, strontium (ΠΙ) ions, calcium (II) ions, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ) Reacting at least one Lewis Sanol selected from the group comprising calcium oxide (CaO), calcium hydroxide (Ca (OH) 2 ), silicon (Si), and silica (Si0 2 ). Also, the terminology used herein is for the purpose of describing particular example embodiments only and is not intended to be limiting of the invention. Singular expressions include plural expressions unless the context clearly indicates otherwise. As used herein, the terms "comprise" and "having" include features, features, steps, configurations, and the like. It is to be understood that the element or combination thereof is intended to be present and does not exclude in advance the possibility of the presence or addition of one or more other features or similarities, steps, components, or combinations thereof.
또한 본 발명에 있어서, 각 층 또는 요소가 각 층들 또는 요소들의 "상에" 또는 "위에" 형성되는 것으로 언급되는 경우에는 각 층 또는 요소가 직접 각 층들 또는 요소들의 위에 형성되는 것을 의미하거나, 다른 층 또는 요소가 각 층 사이, 대상체, 기재 상에 추가적으로 형성될 수 있음을 의미한다.  Also in the present invention, when each layer or element is referred to as being formed "on" or "on" of each layer or element, it means that each layer or element is formed directly on each layer or element, or It is meant that a layer or element can additionally be formed between each layer, on the object, the substrate.
본 발명은 다양한 변경을 가할 수 있고 여러 가지 형태를 가질 수 있는 바, 특정 실시예들을 예시하고 하기에서 상세하게 설명하고자 한다. 그러나， 이는 본 발명을 특정한 개시 형태에 대해 한정하려는 것이 아니며, 본 발명의 사상 및 기술 범위에 포함되는 모든 변경, 균등물 내지 대체물을 포함하는 것으로 이해되어야 한다.  As the invention allows for various changes and numerous modifications, particular embodiments will be illustrated and described in detail below. However, this is not intended to limit the present invention to a specific disclosed form, it should be understood to include all modifications, equivalents, and substitutes included in the spirit and scope of the present invention.
이하, 본 발명을 보다 상세하게 설명한다. 본 발명의 일 측면에 따른 구강 도포용 조성물은 탄닌산 (tannic acid) 및 갈산 (gallic acid)을 포함하는 군에서 선택된 1종 이상의 루이스 염기; 및 철 (II) 이온， 철 (III) 이온, 스트론륨 (III) 이온, 칼슘 (II) 이은, 이산화티타늄 (Ti02), 산화 철 (Fe203), 수산화 철 (Fe(OH)2), 산화 칼슘 (CaO), 수산화 칼슘 (Ca(OH)2), 실리콘 (Si), 및 실리카 (Si02)를 포함하는 군에서 선택된 1종 이상의 루이스 산을 포함한다. 본 발명의 일 실시예에 따르면, 상술한 루이스 염기 및 루이스 산 중 적어도 일부는， 루이스 산에 루이스 염기가 배위된 착화합물의 형태로 존재하는 것일 수 있다. 일반적으로 시린이 증상의 치료에는 증상 발생 부위에 국소적으로 불소를 도포하거나， 레진을 도포하여, 노출된 상아세관을 막는 방법을 사용하며, 최근에는 폴리도파민 (polydopamine)을 활용하여 손상된 에나멜 층의 재생을 촉진시키는 방법에 대한 연구가 진행된 바 있다. Hereinafter, the present invention will be described in more detail. Oral application composition according to an aspect of the present invention comprises at least one Lewis base selected from the group comprising tannic acid (tannic acid) and gallic acid (gallic acid); And iron (II) ions, iron (III) ions, strontium (III) ions, calcium (II) silver, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ), at least one Lewis acid selected from the group consisting of calcium oxide (CaO), calcium hydroxide (Ca (OH) 2 ), silicon (Si), and silica (Si0 2 ). According to one embodiment of the present invention, at least some of the above-described Lewis base and Lewis acid may be present in the form of a complex in which the Lewis base is coordinated with the Lewis acid. In general, in order to treat symptomatic symptom, fluorine or resin is applied locally to prevent the exposure of dentin tubules. Recently, polydopamine is used to remove damaged enamel layer. Research has been conducted on how to promote regeneration.
그러나, 도파민의 경우, 가격이 매우 비싸고, 반웅 조건에 따라 쉽게 산화되어 변질될 수 있으며， 도파민을 치아 표면에 도포한 후 상아세관을 막는 코팅 층이 형성되기까지 시간이 오래 걸리는 문제점이 존재한다. 탄닌산 (tannin acid)은 다양한 식물에서 합성되는 천연 폴리 페놀의 일종으로 하기 화학식의 구조를 가질 수 있다. 그러나, 탄닌산의 분자 구조가 이에 한정되는 것은 아니며, 다양한 작용기를 갖는 다양한 중합체의 형태로 존재할 수 있다. However, in the case of dopamine, the price is very expensive, and it can be easily oxidized and deteriorated according to reaction conditions. There is a problem that takes a long time before the coating layer is formed. Tannin acid is a kind of natural polyphenol synthesized in various plants and may have a structure of the following formula. However, the molecular structure of tannic acid is not limited thereto, and may exist in the form of various polymers having various functional groups.
Figure imgf000009_0001
Figure imgf000009_0001
갈산 (gallic acid) 역시, 비플라보노이드 계열 천연 항산화제의 일종으로， 구조상으로는 3,4，5-트리히드록시벤조산으로 표시될 수 있지만, 실제 천연 상태에서는 다양한 형태의 폴리머 또는 폴리 페놀의 형태로 존재할수 있다. 탄닌산과 갈산은 상술한 구조에서 알 수 있듯이, 분자 내에 많은  Gallic acid is also a non-flavonoid family of natural antioxidants and can be structurally represented as 3,4,5-trihydroxybenzoic acid, but in its natural state it is present in the form of various forms of polymers or polyphenols. can do. Tannic acid and gallic acid, as can be seen in the structure described above,
하이드록시 그룹 또는 카르복시 그룹을 가지고 있기 때문에 다당류, 단백질, 알칼로이드 등의 거대 분자와 쉽게 결합될 수 있다. Since it has a hydroxy group or a carboxy group, it can be easily combined with macromolecules such as polysaccharides, proteins and alkaloids.
특히, 탄닌산 또는 갈산에 존재하는 갈로일 그룹 (galloyl group)은 하이드록入 그룹 또는 카르복시 그룹에 풍부한 비공유 전자쌍으로 인해, 루이스 염기 역할을 할 수 있으며， 철 (II) 이온, 철 (III) 이온, 스트론튬 (III) 이온， 칼슴 (Π) 이온, 이산화티타늄 (Ti02), 산화 철 (Fe203), 수산화 철 (Fe(OH)2), 산화 칼슴 (CaO), 수산화 칼슘 (Ca(OH)2), 실리콘 (Si), 및 실리카 (Si02) 등， 다양한 형태의 루이스 산과 배위 결합을 이루어， 팔면체 구조 등의 안정한 착화합물을 형성할 수 있다. 또한， 각각의 갈로일 그룹이 서로 다른 루이스 산을 중심으로 하여， 가교 결합 (cross link)을 형성할 수 있기 때문에， 고분자 수지와 유사한 형태의 단단한 결합을 형성하여, 치아 표면에도 쉽게 결합될 수 있다. In particular, the galloyl group present in tannic acid or gallic acid can act as a Lewis base, due to the non-covalent electron pairs abundant in the hydroxyl group or the carboxy group, and can be used as iron (II) ions, iron (III) ions, Strontium (III) ions, chalc (Π) ions, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ), chame oxide (CaO), calcium hydroxide (Ca (OH 2 ), silicon (Si), and silica (Si0 2 ) to form coordination bonds with various forms of Lewis acids to form stable complexes such as octahedral structures. In addition, since each galloyl group can form a cross link around a different Lewis acid, it forms a rigid bond similar to that of a polymer resin, and thus can be easily bonded to the tooth surface. .
따라서, 상술한 루이스 산 및 루이스 염기를 포함하는 조성물을 시린이 증상이 나타나는 구강 부위에 국소 도포하는 경우, 조성물 내에 존재할 수 있는 루이스 산에 루이스 염기가 배위된 착화합물이, 외부에 노출된 상아세관의 표면에 코팅 층을 형성하고, 상아세관을 효과적으로 봉쇄할 수 있기 때문에, 효과적으로 시린이 증상을 예방하거나 완화시킬 수 있다.  Therefore, when the composition containing Lewis acid and Lewis base described above is topically applied to the oral cavity where symptom appears, the complex compound coordinated with Lewis base to Lewis acid which may be present in the composition may be Since a coating layer can be formed on the surface and the dentinal tubule can be effectively blocked, the virus can effectively prevent or alleviate the symptoms.
구체적으로, 상기 루이스 산 및 루이스 염기를 포함하는 조성물을 시린이 증상이 나타나는 구강 부위, 즉 상아세관이 노출된 치아에 도포하였을 때, 상술한 착화합물은 손상된 치아의 표면에 약 10nm 내지 약 1 두께, 바람직하게는， 약 20nm 내지 약 500nm 두께로 코팅 층을 형성할 수 있으며, 이로 인하여, 약 0.5 내지 약 2 정도의 직경을 가지는 상아세관을 효과적으로 밀봉할 수 있다ᅳ 상술한 착화합물이 외부에 노출된 상아세관의 표면에 코팅 층을 형성하고 나면, 상기 착화합물의 코팅 층 상에 치아의 주 성분인 하이드록시아파타이트가 침착되어, 하이드록시아파타이트 층이 형성될 수 있다.  Specifically, when the composition comprising Lewis acid and Lewis base is applied to the oral cavity where symptom appears, that is, the teeth exposed to ivory tubules, the above-described complex is about 10 nm to about 1 thick on the surface of the damaged tooth, Preferably, the coating layer may be formed to a thickness of about 20 nm to about 500 nm, thereby effectively sealing the ivory tubule having a diameter of about 0.5 to about 2 상. After the coating layer is formed on the surface of the tubules, hydroxyapatite, the main component of the tooth, is deposited on the coating layer of the complex, thereby forming a hydroxyapatite layer.
타액 및 치아 표면에 포함된 칼슘 및 인 성분 등은 탄닌산 또는 갈산 분자의 내부에 존재하는 많은 작용기들로 인하여, 상기 착화합물 코팅 층 상에 쉽게 침착될 수 있으며, 이로 인해 하이드록시아파타이트 층이 상술한 착화합물 코팅 층 상에 쉽게 형성될 수 있다.  The saliva and calcium and phosphorus components contained in the tooth surface can be easily deposited on the complex coating layer due to the many functional groups present inside the tannic acid or gallic acid molecules, which causes the hydroxyapatite layer to be described above. It can be easily formed on the coating layer.
이러한 하이드록시아파타이트 층에 의해 노출되었던 상아세관이 완전히 봉쇄될 수 있으며, 치아의 손상된 부분 등이 원래 치아의 형태와 유사하게 재생될 수 있다. 탄닌산 또는 갈산은 포도, 감， 밤, 도토리， 녹차, 등 천연 식품에 다량으로 존재하며, 수 천년 간 인체에 흡수되어온 폴리 페놀 물질로, 인체에 대한 안전성이 어느 정도 확립되어 있다.  The dentin tubules that were exposed by this hydroxyapatite layer can be completely blocked, and damaged parts of the teeth can be regenerated similar to the shape of the original teeth. Tannic acid or gallic acid is present in a large amount in natural foods such as grapes, persimmons, chestnuts, acorns, green tea, and the like, and is a polyphenol material that has been absorbed by the human body for thousands of years.
탄닌산 또는 갈산은 천연물로 쉽게 얻을 수 있고, 공업적으로는 목재를 가공하고 남은 나무 껍질 등에서 쉽게 추출할 수 있기 때문에, 가격 경쟁력 역시 매우 우수하다. 또한, 상기 조성물을 구강에 도포하는 경우, 처음에는 탄닌산 또는 갈산의 분자 또는 작은 단위의 상술한 착화합물 분자들이 치아의 표면에 흡착되고， 이어서 다른 탄닌산 또는 갈산 분자， 상술한 루이스 산 물질, 혹은 상술한 착화합물 분자와 가교 결합 (cross linking)을 형성하면서 , 치아의 표면에 코팅 층을 형성하게 된다. Tannic acid or gallic acid can be easily obtained as a natural product, and industrially, wood can be easily extracted from the remaining bark and the like, so the price is also very excellent. In addition, when the composition is applied to the oral cavity, initially a molecule of tannic acid or gallic acid or a small unit of the above-mentioned complex compound molecules is adsorbed onto the surface of the tooth, followed by other tannic acid or gallic acid molecules, the Lewis acid material described above, or While forming cross linking with the complex molecule, a coating layer is formed on the surface of the tooth.
따라서, 상기 조성물을 용액 등의 형태로 구강 내에 도포하는 것만으로도 효과적으로 상아세관을 밀봉하여, 시린이 증상을 방지하거나 완화시킬 수 있으며, 이러한 코팅 층의 형성은 구강 내 도포 후 약 5분 내지 10분 이내에 매우 빠르게 일어나기 때문에 치과 치료 등에 매우 용이하게 적용될 수 있다.  Therefore, simply applying the composition in the form of a solution, etc. in the oral cavity effectively seals the dentinal tubule, so that the symptom can prevent or alleviate the symptoms, the formation of such a coating layer is about 5 minutes to 10 minutes after application in the oral cavity It occurs very quickly within minutes, so it can be easily applied to dental care.
또한, 구강 내 환경 조건에서는 위 가교 결합이 쉽게 분해되지 않기 때문에 내구성이 매우 우수하여， 치료에 의한 효과 지속 기간이 매우 긴 장점이 있다. 상기 루이스 염기 및 루이스 산의 착화합물은 2배위 착화합물, 4배위 착화합물, 및 6배위 착화합물로 이루어진 군에서 선택된 1종 이상을 포함하는 것일 수 있다.  In addition, in the oral environment, gastric crosslinks are not easily decomposed, so the durability is very excellent, and the effect duration of treatment is very long. The complex of the Lewis base and the Lewis acid may include one or more selected from the group consisting of a double coordination complex, a fourth coordination complex, and a six coordination complex.
2배위 착화합물 (mono-complex)은 상술한 루이스 산에 루이스 염기 중 The coordination complex (mono-complex) is a Lewis base in Lewis acid as described above.
2개의 하이드록실 그룹이 배위되어 리간드를 형성하고 있는 것을 의미하고, 4배위 착화합물 (bis-complex)은 루이스 산에 상술한 루이스 염기 중 4개의 하이드록실 그룹이 배위되어 리간드를 형성하고 있는 것을 의미하고, 6배위 착화합물 (tris- complex)은 루이스 산에 상술한 루이스 염기 중 6개의 하이드록실 그룹이 배위되어 리간드를 형성하고 있는 것을 의미한다. Means that two hydroxyl groups are coordinated to form a ligand, and a bi-complex complex means that four hydroxyl groups of the Lewis bases described above are coordinated with Lewis acid to form a ligand. , 6 coordination complex (tris-complex) means that six hydroxyl groups of Lewis bases mentioned above are coordinated with Lewis acid to form a ligand.
그러나， 본 발명이 반드시 이에 한정되는 것은 아니며， 루이스 산으로 사용되는 물질의 종류에 따라 다양한 형태 및 구조를 갖는 착화합물이 형성될 수 있다.  However, the present invention is not necessarily limited thereto, and complex compounds having various forms and structures may be formed according to the type of material used as the Lewis acid.
특히， 루이스 산으로 철 (II) 이온， 철 (III) 이온, 스트론튬 (III) 이온， 및 /또는 칼슘 (II) 이온 둥이 사용되는 경우에는， 이러한 금속 이온이 중심 금속이 되어 착화합물을 형성할 수 있으며, 이산화티타늄 (Ti02), 산화 철 (Fe203), 수산화 철 (Fe(OH)2), 산화 칼슴 (CaO), 수산화 칼슴 (Ca(OH)2), 실리콘 (Si), 및 /또는 In particular, when Lewis (I) ions, iron (III) ions, strontium (III) ions, and / or calcium (II) ions are used as Lewis acids, these metal ions may become central metals to form complexes. Titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ), chalc oxide (CaO), chalc hydroxide (Ca (OH) 2 ), silicon (Si), and /or
실리카 (Si02) 등이 루이스 산으로 사용되는 경우에는, 이러한 물질들의 나노 사이즈 입자 (nano particle)에 상술한 루이스 염기의 하이드톡시 그룹이 배위되어 착화합물을 형성할 수도 있다. 상술한 나노 사이즈 입자는, 약 10nm 내지 약 1 의 입경을 가진 것일 수 이러한 착화합물은, 좀 더 구체적으로 예를 들어, 하기 구조식의 형태를 있다. · Silica (Si0 2) may be such a case that is used as a Lewis acid include, these hydroxy-ethoxy group of the Lewis base described above to nano-size particles (particle nan o) of the material is to form a coordination complex. The nano-size particles described above may have a particle size of about 10 nm to about 1, and such complex compounds are more specifically, for example, in the form of the following structural formula. ·
Figure imgf000012_0001
Figure imgf000012_0001
상기 구조식에서 Me는 루이스 산으로 철 (II) 이온， 철 (III) 이온, 스트론튬 (III) 이온, 및 /또는 칼슘 (II) 이온 등이 사용되어， 착화합물의 중심에 금속 이은 등이 위치하는 경우를 의미하며, Nano Particle은, 이산화티타늄 (Ti02), 산화 철 (Fe203), 수산화 철 (Fe(OH)2), 산화 칼슘 (CaO), 수산화 칼슴 (Ca(OH)2), 실리콘 (Si), 및 /또는 실리카 (Si02) 등의 나노 사이즈 입자가 루이스 산으로 사용되어, 착화합물의 중심에 이러한 물질들의 나노 사이즈 입자 (nano particle)가 위치하고, 여기에 상술한 루이스 염기의 하이드록시 그룹이 배위되는 것을 의미한다. 그러나 본 발명에서 사용되는 착화합물이 반드시 상술한 구조식에 한정되는 것은 아니며, 사용되는 루이스 산 및 루이스 염기의 종류에 따라, 다양한 구조 및 배위수를 가지는 착화합물로 이루어질 수 있다. In the above structural formula, Me is a Lewis acid in which iron (II) ions, iron (III) ions, strontium (III) ions, and / or calcium (II) ions are used. Nano Particle, titanium dioxide (Ti0 2 ), oxidation Nanoparticles such as iron (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ), calcium oxide (CaO), calamus hydroxide (Ca (OH) 2 ), silicon (Si), and / or silica (Si0 2 ) Size particles are used as Lewis acids, meaning that nano-size particles of these materials are located in the center of the complex, where the hydroxy groups of the Lewis bases described above are coordinated. However, the complex used in the present invention is not necessarily limited to the above-described structural formula, and may be composed of complex compounds having various structures and coordination numbers, depending on the type of Lewis acid and Lewis base used.
상기 구조식에서 각각의 갈로일 그룹은, 같은 탄닌산 또는 갈산 분자에 속하는 킬레이트 형태일 수도 있고, 다른 탄닌산 또는 갈산 분자에 속하는 것으로 이웃한 착화합물과 가교 결합을 형성하고 있는 것일 수도 있다. 또한, 상기 착화합물들은 조성물 상태 및 구강에 도포된 상태에서, 온도 , ρΗ 등의 외부 조건에 따라 서로 흔재되어 있을 수 있다.  Each galloyl group in the above structural formula may be in the form of a chelate belonging to the same tannic acid or gallic acid molecule, or may belong to another tannic acid or gallic acid molecule and form a crosslink with a neighboring complex compound. In addition, the complex compounds may be common to each other depending on external conditions such as temperature, ρΗ, etc., in the state of the composition and the state applied to the oral cavity.
본 발명의 일 실시예에 따르면, 상기 조성물은 상기 루이스 염기 및 상기 루이스 산을 각각 약 img/ml 내지 약 lmg/ml 의 농도로 포함하는 것일 수 있다. 루이스 염기 및 상기 루이스 산의 농도가 상기 범위보다 낮은 경우， 생성되는 착화합물의 양이 층분하지 못하여， 코팅 층이 층분히 형성되지 않는 문제점이 발생할 수 있다. 그러나 본 발명이 반드시 이에 한정되는 것은 아니며， 상기 루이스 염기 및 루이스 산의 농도는 시린이 치료 및 방지용으로 적용 시, 적용 부위 및 적용 조건에 따라 달라질 수 있다.  According to an embodiment of the present invention, the composition may include the Lewis base and the Lewis acid in a concentration of about img / ml to about lmg / ml, respectively. When the concentration of the Lewis base and the Lewis acid is lower than the above range, the amount of the complex compound to be produced may not be divided, and the coating layer may not be formed. However, the present invention is not necessarily limited thereto, and the concentration of the Lewis base and the Lewis acid may vary depending on the application site and the application conditions when the vaccine is applied for treatment and prevention.
또한, 상기 조성물은 상기 루이스 염기 및 상기 루이스 산을 약 0.5:1 내지 약 10:1의 몰 비율로 포함하는 것이 바람직할 수 있다. 루이스 염기 및 상기 루이스 산의 몰 비율이 상기 범위보다 낮은 경우, 루이스 염기의 양이 양이 층분치 못하여， 루이스 산에 많은 비공유 전자쌍을 제공하지 못해 가교 결합이 층분히 형성되지 못하는 문제점이 발생할 수 있고， 루이스 염기 및 상기 루이스 산의 몰 비율이 상기 범위보다 높은 경우, 반대로 착화합물의 중심이 되는 루이스 산의 양이 적어, 가교 결합이 층분히 형성되지 못하는 문제점이 발생할 수 있다. 발명의 또 다른 일 실시예에 따르면, 상기 조성물은 pH가 약 3 내지 약 8 범위인 것이 바람직할 수 있으며, 약 6 내지 약 7.6 범위인 것이 더욱 바람직할 수 있다. 이러한 pH 범위는 구강 내의 환경과 유사한 산도를 갖는 범위이기도 하지만, 상기 pH 범위에서 상술한 착화합물은 4배위 내지 10배위 또는 4배위 내지 6배위의 착화합물 형태로 존재하게 되어， 단단한 가교 결합을 형성 및 유지할 수 있다 · ρΗ가 상기 범위보다 낮은 경우, 높은 수소 이온 농도로 인하여, 갈로일 그룹의 하이드록실 그룹이 착화합물의 중심 루이스 산에 리간드를 제공하지 못하게 되어， 가교 결합이 효과적으로 형성되지 못하는 문제점이 발생할 수 있다. 또한 , ρΗ가 상기 범위보다 높은 경우, 높은 수산화 이온의 농도로 인하여 수산화 이온이 상술한 루이스 산에 비공유 전자쌍을 제공할 가능성이 In addition, the composition may preferably comprise the Lewis base and the Lewis acid in a molar ratio of about 0.5: 1 to about 10: 1. If the molar ratio of the Lewis base and the Lewis acid is lower than the above range, the amount of Lewis base may not be sufficient in amount, and thus, a large amount of unshared electron pairs may not be provided to the Lewis acid, and crosslinking may not be formed in a sufficient amount. When the molar ratio of the Lewis base and the Lewis acid is higher than the above range, the amount of Lewis acid, which is the center of the complex compound, may be less, and crosslinking may not be sufficiently formed. According to another embodiment of the invention, the composition may preferably have a pH in the range of about 3 to about 8, more preferably in the range of about 6 to about 7.6. This pH range is also a range having an acidity similar to the environment in the oral cavity, but the complex compound described above in the pH range is 4 to 10 or 4 coordination. Can be present in the form of a complex of 6 to 6 coordination to form and maintain a rigid crosslink. · When ρΗ is lower than the above range, due to the high hydrogen ion concentration, the hydroxyl group of the galloyl group is present in the central Lewis acid of the complex. Failure to provide ligands can lead to problems in which crosslinking cannot be effectively formed. In addition, when ρΗ is higher than the above range, it is likely that the hydroxide ions will provide the lone pair with the above-mentioned Lewis acid due to the high concentration of hydroxide ions.
높아지게되며， 따라서, 가교 결합이 효과적으로 형성되지 못하는 문제점이 발생할 수 있다. As a result, a problem may occur in that a crosslink cannot be effectively formed.
상기 ρΗ 범위 조절을 위해서는 인산 완층 식염수 (posphate buffered saline, PBS), 트리스 완층용액 (tris(hydroxymethyl)aminomethane-HCl), 및 /또는 수산화 나트륨 수용액 (NaOH) 등을 사용할 수 있다.  To adjust the ρΗ range, phosphate buffered saline (PBS), tris (hydroxymethyl) aminomethane-HCl, and / or sodium hydroxide aqueous solution (NaOH) may be used.
발명의 일 실시예에 따르면， 상기 조성물은 별도의 실리카 입자를 더 포함할 수도 있다. 여기서 말하는 실리카 입자는, 상기 조성물의 루이스 산으로 사용되어, 탄닌산 또는 갈산과 착화합물을 형성하는 나노 사이즈의 실리카 외에， 별도로 더 포함되는 것을 말한다.  According to one embodiment of the invention, the composition may further comprise separate silica particles. The silica particles referred to herein are used as Lewis acids of the composition and are further included separately in addition to the nano-sized silica which forms a complex with tannic acid or gallic acid.
실리카 입자는 상술한 가교 결합 형성 과정에서, 착화합물에 의한 코팅 층 형성을 위한 핵으로 작용할 수 있으며, 상기 착화합물에 의해 표면이 코팅되어, 시린이 치료 등에 적용 시， 치아의 손실 부분을 메꿀 수 있는 층진체의 역할을 할 수 있다. 상술한 착화합물에 의해 표면이 코팅된 실리카 입자가 상아세관 내에 침투되어 상아세관을 봉쇄할 수 있으며， 그 위로 상술한 하이드록시아파타이트 층이 형성되어 손상된 치아 부분을 재생시킬 수 있다.  Silica particles may act as a nucleus for forming a coating layer by a complex compound in the above-described crosslink formation process, and the surface may be coated by the complex compound to fill a loss part of a tooth when a syringe is used for treatment or the like. Can play a role in the body. Silica particles coated on the surface by the above-described complex compound may penetrate into the dentin tubules to block the dentin tubules, and the hydroxyapatite layer described above may be formed to regenerate damaged tooth portions.
이러한 실리카 입자는, 수평균 입경이 약 0.05 m 내지 약 5 인 것이 바람직할 수 있다. 실리카 입자의 수평균 입경이 상기 범위보다 작은 경우， 착화합물에 의해 표면 코팅이 쉽게 일어나지 않을 수 있으며, 상기 범위보다 큰 경우, 실리카 입자가 상아세관 침투하지 못하는 문제점이 발생할 수 있다. 그러나 본 발명이 반드시 이에 한정되는 것은 아니다.  Such silica particles may preferably have a number average particle diameter of about 0.05 m to about 5. When the number average particle diameter of the silica particles is smaller than the above range, the surface coating may not easily occur due to the complex compound. If the number average particle diameter of the silica particles is larger than the above range, the silica particles may not penetrate into the ivory tubule. However, the present invention is not necessarily limited thereto.
그리고, 상기 실리카 입자는 조성물 전체에 대해 약 50 중량% 이하로 포함되는 것이 바람직할 수 있다.  In addition, the silica particles may be preferably included in about 50% by weight or less based on the total composition.
부가하여， 상술한 조성물의 경우， 구강 내에 도포되더라도， 치아의 색상 변화가 심하게 이루어지지 않기 때문에, 심미적 측면에서도 우수한 효과를 얻을 수 있다. In addition, in the case of the above-described composition, even if applied in the oral cavity, since the color change of the tooth is not made severely, an excellent effect can also be obtained in aesthetic aspect. Can be.
특히, 상술한 조성물은, 구강 내에 도포하였을 때 하기 수학식 1로  In particular, the above-described composition, when applied in the oral cavity by the following formula (1)
계산되는 ΔΕ 값이 약 3 내지 약 25의 범위, 바람직하게는 약 3 내지 약 15의 범위, 더욱 바람직하게는 약 3 내지 약 6의 범위에 있어， 처리 전 후， 육안으로는 식별하기 힘든 정도의 색상 변화만을 가져오거나， 색상 변화가 거의 없을 수 있다.The calculated ΔΕ value is in the range of about 3 to about 25, preferably in the range of about 3 to about 15, more preferably in the range of about 3 to about 6, and is difficult to visually identify before and after treatment. Only the color change may be brought or there may be little color change.
수학식 1] Equation 1]
Figure imgf000015_0001
Figure imgf000015_0001
또한， 상술한 조성물은, 구강 내에 도포하였을 때, 하기 수학식 2 및 3에 의해 계산되는 AW* 값이 약 -7 내지 20의 범위, 바람직하게는 약 0 내지 약 20의 범위, 더욱 바람직하게는 약 2 내지 6의 범위에 있어, 치아의 미백 지수가  In addition, the composition described above, when applied in the oral cavity, the AW * value calculated by the following equations (2) and (3) is in the range of about -7 to 20, preferably in the range of about 0 to about 20, more preferably In the range of about 2 to 6, the teeth whitening index is
육안으로 식별하기 힘든 정도의 변화만을 가져오거나, 오히려, 치아가 밝아지게 되어, 별도의 미백 시술 없이도， 치아 미백 효과를 얻을 수 있게 된다. Only a change of degree which is hard to discern with the naked eye is brought about, or, rather, the teeth become brighter, so that a whitening effect of the teeth can be obtained without a separate whitening procedure.
[수학식 2]  [Equation 2]
W* = {(a*)2 + (b*)2 + (L* - 100)2]1/2 W * = {(a * ) 2 + (b * ) 2 + (L * -100) 2 ] 1/2
[수학식 3]  [Equation 3]
AW* - W* ( af ter ) - W* (bef ore )  AW *-W * (af ter)-W * (bef ore)
또한, 상기 조성물은 가글액이나 도포액 등의 용액, 치약이나 연고 등으로 적용될 수 있는 페이스트， 분사액 등으로 적용이 가능한 에어로졸, 또는  In addition, the composition is aerosol, which can be applied as a solution such as gargle or coating liquid, paste, spray solution, etc. which can be applied as toothpaste or ointment, or
도포용으로 사용할 수 있는 레진 형태의 제형을 가질 수 있다. It may have a formulation in the form of a resin that can be used for application.
가글액으로 제조하는 경우, 환자가 직접 가글액을 수십 초 내지 수 분 동안 입에 머금은 후, 행구어내는 방법을 반복함으로써, 쉽게 시린이를 치료하고， 방지할 수 있다.  In the case of preparation of the gargle, the patient directly holds the gargle in the mouth for several tens of seconds and then repeats the method of rinsing, thereby easily treating and preventing the syringe.
도포액 또는 연고의 형태로 제조하는 경우, 치과 의사가 직접 환부에 도포하는 것만으로도 처치하는 것이 가능하며, 레진의 형태로 제조되는 경우, 시린이 증상이 나타나는 치아의 손상 부분 등에 상기 레진을 도포하고  In the case of manufacturing in the form of a coating liquid or ointment, it is possible to be treated by the dentist directly applying to the affected area, and in the case of the resin, the resin is applied to the damaged part of the tooth where the symptom is symptomatic. and
경화시키는 방법을 통한 처치가 가능하다. Treatment is possible through curing.
치약의 형태로 제조하는 경우는, 치약의 일 성분으로 상술한 조성물이 포함되어， 이러한 치약을 사용하여 잇솔질을 반복함으로써 시린이 증상의 치료 및 방지가 가능하다. When prepared in the form of toothpaste, the composition described above as one component of the toothpaste It is possible to treat and prevent symptomatic symptoms by repeating brushing with such toothpaste.
그러나， 본 발명이 이에 한정되는 것은 아니며, 본 발명이 속하는 기술 분야에서 일반적으로 채용되는 형태의 제형으로 가공되어 시린이 치료 및 방지용으로 적용할 수 있음은 물론이다. 한편, 본 발명의 또 다른 일 측면에 따른 구강 도포용 조성물의 제조 방법은, 탄닌산 (tannic acid) 및 갈산 (gallic acid)을 포함하는 군에서 선택된 1종 이상의 루이스 염기; 및 철 (Π) 이온, 철 (III) 이온, 스트론튬 (III) 이온, 칼슘 (II) 이온, 이산화티타늄 (Ti02), 산화 철 (Fe203), 수산화 철 (Fe(OH)2), 산화 칼슘 (CaO), 수산화 칼슘 (Ca(OH)2), 실리콘 (Si), 및 실리카 (Si02)를 포함하는 군에서 선택된 1종 이상의 루이스 산;을 반웅시키는 단계를 포함한다. However, the present invention is not limited thereto, and it is a matter of course that the aline can be applied to the treatment and prevention by processing the formulation of a form generally employed in the art. On the other hand, a method for producing a composition for oral application according to another aspect of the present invention, at least one Lewis base selected from the group comprising tannic acid (tannic acid) and gallic acid (gallic acid); And iron (Π) ions, iron (III) ions, strontium (III) ions, calcium (II) ions, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe (OH) 2 ) And at least one Lewis acid selected from the group consisting of calcium oxide (CaO), calcium hydroxide (Ca (OH) 2 ), silicon (Si), and silica (Si0 2 ).
반웅 시, 반웅 방법은 특별히 한정되지 않으며, 예를 들어, 루이스 염기 및 루이스 산 각각의 수용액을 제조한 후, 이를 흔합하여 교반하는 것 만으로도 반웅을 진행시킬 수 있다.  At the time of reaction, the reaction method is not particularly limited, and for example, after preparing an aqueous solution of each of Lewis base and Lewis acid, the reaction can be advanced simply by mixing and stirring the mixture.
그리고, 상술한 루이스 산으로 금속 이온이 사용되는 경우， 이러한 금속 이온을 발생시키기 위한 전구체로 다양한 금속 염이 사용될 수 있다.  In addition, when metal ions are used as the Lewis acid described above, various metal salts may be used as precursors for generating the metal ions.
상기 반응 단계에 있어서 루이스 염기 및 루이스 산은 0.5:1 내지 10: 1의 몰 비율로 흔합하여 반응시키는 것이 바람직할 수 있으며， 이러한 비율 한정에 대한 설명은 상기 조성물에서 설명한 바와 같다.  In the reaction step, the Lewis base and the Lewis acid may be preferably reacted by mixing in a molar ratio of 0.5: 1 to 10: 1, and the description of the ratio limitation is as described in the composition.
또한， 상기 반응시키는 단계는 pH가 3 내지 7.5 범위에서 수행되는 것이 바람직할 수 있으며, 이러한 pH의 한정 이유 역시 상기 조성물에서 설명한 바와 같다.  In addition, the step of reacting may be preferably performed in a pH range of 3 to 7.5, the reason for limiting such pH is also as described in the composition.
상기 반웅시키는 단계는 4 내지 60°C의 온도 범위 및 0.1 내지 5atm의 압력 범위 하에서 수행되는 것이 바람직할 수 있고， 15 내지 40°C의 온도 범위 및 0.1 내지 2atm의 압력 범위 하에서 수행되는 것이 더욱 바람직할 수 있으며, 구강 내부와 비슷한 환경인 30 내지 40°C의 온도 범위 및 0.5 내지 1.5atm의 압력 범위 하에서 수행되는 것이 가장 바람직할 수 있으나， 본 발명이 반드시 이에 한정되는 것은 아니며， 상술한 조건이나 기구의 제약 없이 수행하는 것이 가능하다. The reaction may be performed under a temperature range of 4 to 60 ° C and a pressure range of 0.1 to 5 atm, and more preferably performed under a temperature range of 15 to 40 ° C and a pressure range of 0.1 to 2 atm. And, it may be most preferably performed under a temperature range of 30 to 40 ° C and a pressure range of 0.5 to 1.5 atm, which is a similar environment as the oral cavity, the present invention is not necessarily limited thereto, It is possible to perform without the constraints of the instrument.
또한, 이 외에 상기 반응의 생성물인 착화합물로 실리카 입자를 코팅하는 단계를 더 포함할 수도 있다. 코팅 방법은 특별히 제한되지 않으며, 예를 들어 루이스 염기 및 루이스 산 각각의 수용액을 흔합한 조성물에 상술한 실리카 입자가 고르게 분산되도록 침지시키는 것만으로, 표면이 코팅된 실리카 입자를 얻을 수 있다. 발명의 다른 일 측면에 따르면, 상기 구강 도포용 조성물을 상아세관이 노출된 구강 내부에 도포하여 코팅층을 형성하는 단계를 포함하는, 상아세관 밀봉 방법이 제공될 수 있다. In addition, in addition to coating the silica particles with a complex compound that is a product of the reaction It may further comprise a step. The coating method is not particularly limited, and for example, the surface-coated silica particles can be obtained only by immersing the aqueous solution of each of the Lewis base and Lewis acid so as to evenly disperse the above-described silica particles in a mixed composition. According to another aspect of the invention, the ivory tubule sealing method comprising the step of forming a coating layer by applying the composition for oral application in the oral cavity exposed to the dentin tube can be provided.
그리고, 상기 상아세관 밀봉 방법은, 상기 코팅충 상에,  And, the ivory capillary sealing method, on the coating
하이드록시아파타이트 층을 형성하는 단계를 더 포함할 수도 있으며, 이에 대한 내용은 구강 도포용 조성물의 설명 부분에서 상술한 바와 같다. 이하, 발명의 구체적인 실시예를 통해, 발명의 작용 및 효과를 보다 상술하기로 한다. 다만, 이러한 실시예는 발명의 예시로 제시된 것에 불과하며, 이에 의해 발명의 권리범위가 정해지는 것은 아니다. The method may further include forming a hydroxyapatite layer, which is described above in the description of the composition for oral application. Hereinafter, the operation and effects of the invention will be described in more detail with reference to specific examples of the invention. However, these embodiments are only presented as an example of the invention, whereby the scope of the invention is not determined.
<실시예 > <Example>
치아시편의 준비  Preparation of Dental Specimen
발치된 지 3개월 이내의 대구치로, 치아우식증 및 수복물이 없는 치아를 준비하였다. 발치된 치아는 시험 전까지 l% chloramine T 용액에 보관하였다. 저속 다이아몬드 롭을 이용하여 상기 치아의 치관부를 제거하고, 상아질이 노출되도록 lmm 두께로 절단하여 치아 시편을 준비하였다. 절단면은 사포를 이용하여 3000 매쉬까지 경면 연마하였으며， 시편은 초음파 세척기에서 아세톤， 에탄올， 증류수의 순서로 세척한 후 상온에서 건조하였다.  With molars within three months of extraction, teeth without caries and restorations were prepared. Extracted teeth were stored in l% chloramine T solution until testing. A tooth specimen was prepared by removing the crown of the tooth using a low-speed diamond rob and cutting it to lmm thickness to expose the dentin. The cut surface was mirror polished up to 3000 mesh using sandpaper, and the specimen was washed in the order of acetone, ethanol and distilled water in an ultrasonic cleaner and dried at room temperature.
준비된 시편에 대해 그 일부를 채취한 후， SEM을 이용하여 그 표면 및 단면을 관찰하였다.  After taking a part of the prepared specimens, the surface and the cross section were observed by SEM.
도 1은 상기에서 준비된 치아 시편 표면의 여러 부분을 배율을 달리하여 관찰한 SEM 이미지이다.  FIG. 1 is an SEM image of various parts of the prepared surface of the dental specimen at different magnifications.
도 1을 참조하면， 시편의 표면에 상아세관이 노출된 것을 확인할 수 있다. 도 2는 상기에서 준비된 치아 시편의 다양한 단면에 대해 다른 배율로 관찰한 SEM 이미지이다. Referring to Figure 1, it can be seen that the ivory tubules are exposed on the surface of the specimen. Figure 2 shows different magnifications for various cross sections of the prepared dental specimens. The observed SEM image.
도 2를 참조하면, 치아 시편의 표면 등이 손상되어 울통불통한 요철이 형성되어 있음을 확인할 수 있다 (우 상). 구강도포용 조성물의 제조  Referring to Figure 2, it can be seen that the surface of the tooth specimen is damaged, so that uneven depressions are formed (upper right). Preparation of oral application composition
[실시예 1] Example 1
0.8mg/ml 농도의 탄닌산 수용액과 0.2mg/ml 농도의 염화철 (FeCl3, 시그마 알드리치) 수용액을 각각 준비하였다. 상기 수용액을 각각 5ml씩 흔합한 후 , ρΗ가 7이상이 될 때까지 인산 완층 용액을 점적하여, 탄닌산 및 철 (III) 이온의 An aqueous solution of tannic acid at a concentration of 0.8 mg / ml and an aqueous solution of iron chloride (FeCl 3 , Sigma Aldrich) at a concentration of 0.2 mg / ml were prepared, respectively. After mixing 5 ml of each of the above aqueous solutions, the complete phosphate solution was added dropwise until ρΗ was 7 or more to obtain tannin and iron (III) ions.
착화합물을 포함하는 조성물을 제조하였다. A composition comprising a complex compound was prepared.
[실시예 2] Example 2
상기 실시예 1에서 제조된 조성물에 평균 입경이 50 내지 lOOnm 인 실리카 입자 (시그마 알드리치)를 첨가하였다. 상기 실시예 1의 조성물:실리카 입자가 10: 1의 중량비가 되도록 첨가하였으며, 실리카 입자가 고루 분산되도록 교반하였다. SEM을 이용하여 탄닌산-철 (III) 착화합물이 코팅된 실리카 입자를 관찰하였다.  Silica particles (Sigma Aldrich) having an average particle diameter of 50 to 100 nm were added to the composition prepared in Example 1. The composition of Example 1: Silica particles were added in a weight ratio of 10: 1, and the silica particles were stirred to disperse evenly. SEM particles were used to observe silica particles coated with the tannin-iron (III) complex.
도 6은 일반 실리카 입자 및 상기 실시예 2에서 제조된 조성물을 관찰한 SEM 이미지이다.  6 is an SEM image of ordinary silica particles and the composition prepared in Example 2 above.
도 6을 참조하면, 좌측의 일반 실리카 입자에 비해， 우측의 실리카 입자는 그 표면에 상대적으로 투명한 막이 생성된 것을 확인할 수 있으며, 이러한 막은 탄닌산-철 (III) 착화합물이 실리카 입자 표면 상에 침착되어 코팅 층을 형성한 것으로 해석할 수 있다.  Referring to FIG. 6, compared to the general silica particles on the left side, the silica particles on the right side can be seen that a relatively transparent film is formed on the surface thereof, and this film is formed by depositing a tannic acid-iron (III) complex on the surface of the silica particles. It can be interpreted as forming a coating layer.
[실시예 3] Example 3
0.8mg/ml 농도의 탄닌산 수용액과， 0.2mg/ml 농도의 이산화티타늄 (Ή02) 나노입자 (입경 : 10nm 내지 1卿, 제조사: 시그마 알드리치) 수분산액을 준비하였다. 상기 수용액 및 수분산액을 각각 5ml씩 흔합한 후, pH가 7이상이 될 때까지 인산 완충 용액을 점적하여, 탄닌산 및 이산화티타늄 나노입자의 착화합물을 포함하는 조성물을 제조하였다. An aqueous solution of tannic acid at a concentration of 0.8 mg / ml and an aqueous dispersion of titanium dioxide (Ή0 2 ) nanoparticles (particle size: 10 nm to 1 卿, manufacturer: Sigma Aldrich) at 0.2 mg / ml were prepared. After mixing 5 ml of each of the aqueous solution and the aqueous dispersion, and then dropping the phosphate buffer solution until the pH is 7 or more, the tannin acid and titanium dioxide nanoparticles A composition comprising a complex compound was prepared.
[실시예 4] Example 4
0.8mg/ml 농도의 탄닌산 수용액과, 0.2mg/ml 농도의 질산  Tannic acid solution at 0.8 mg / ml concentration and nitric acid at 0.2 mg / ml concentration
스트론튬 (Sr(N03)2) 수용액을 준비하였다. Strontium (Sr (N0 3 ) 2 ) aqueous solution was prepared.
상기 수용액을 각각 5ml씩 흔합한 후 , ρΗ가 7이상이 될 때까지 인산 완층 용액을 점적하여, 탄닌산 및 스트론튬 이온의 착화합물을 포함하는 조성물을 제조하였다. [실시예 5]  After mixing 5 ml of each of the above aqueous solutions, a complete phosphoric acid solution was added dropwise until ρΗ was 7 or more to prepare a composition including a complex of tannic acid and strontium ions. Example 5
0.8mg/ml 농도의 탄닌산 수용액과, 0.2mg/ml 농도의 실리카 (Si02) Tannic acid solution at 0.8 mg / ml concentration and silica at 0.2 mg / ml concentration (Si0 2 )
나노입자 (입경 : 10nm 내지 ffli, 제조사: 시그마 알드리치) 수분산액을 준비하였다. 상기 수용액 및 수분산액을 각각 5ml씩 흔합한 후 , ρΗ가 7이상이 될 때까지 인산 완층 용액을 점적하여, 탄닌산 및 실리카 나노입자의 착화합물을 포함하는 조성물을 제조하였다. A nanoparticle (particle diameter: 10 nm to ffli, manufacturer: Sigma Aldrich) was prepared with an aqueous dispersion. After mixing 5 ml of each of the aqueous solution and the aqueous dispersion, and then dropping the complete phosphate solution until ρΗ was 7 or more, a composition including a complex compound of tannic acid and silica nanoparticles was prepared.
[실시예 6] Example 6
0.8mg/ml 농도의 탄닌산 수용액과, 0.2mg/ml 농도의 산화 철 (Fe203) 나노입자 (입경 : 10nm 내지 Ιμπι, 제조사: 시그마 알드리치) 수분산액을 준비하였다. 상기 수용액 및 수분산액을 각각 5ml씩 흔합한 후 , ρΗ가 7이상이 될 때까지 인산 완층 용액을 점적하여, 탄닌산 및 산화 철 나노입자의 착화합물을 포함하는 조성물을 제조하였다. An aqueous solution of tannin acid at a concentration of 0.8 mg / ml and an aqueous dispersion of iron oxide (Fe 2 O 3 ) nanoparticles (particle size: 10 nm to Ιμπι, manufactured by Sigma Aldrich) at a concentration of 0.2 mg / ml were prepared. After mixing 5 ml of each of the aqueous solution and the aqueous dispersion, and then dropping the complete phosphate solution until ρΗ is 7 or more, a composition containing a complex compound of tannic acid and iron oxide nanoparticles was prepared.
[실시예 7] Example 7
0.8mg/ml 농도의 탄닌산 수용액과 , 0.2mg/ml 농도의 수산화 칼슘 (Ca (OH)2) 나노입자 (입경 : 10nm 내지 1//II1, 제조사: 시그마 알드리치) 수분산액을 준비하였다. 상기 수용액 및 수분산액을 각각 5ml씩 흔합한 후 , ρΗ가 7이상이 될 때까지 인산 완충 용액을 점적하여, 탄닌산 및 수산화 칼슘 나노입자의 An aqueous solution of tannin acid at a concentration of 0.8 mg / ml and a calcium hydroxide (Ca (OH) 2 ) nanoparticle (particle size: 10 nm to 1 // II1, manufactured by Sigma Aldrich) at 0.2 mg / ml were prepared. After mixing 5 ml of each of the aqueous solution and the aqueous dispersion, and then dropping the phosphate buffer solution until ρΗ is 7 or more, the tannin acid and calcium hydroxide nanoparticles
착화합물을 포함하는 조성물을 제조하였다. [실시예 1-1, 및 실시예 3-1 내지 7-1] A composition comprising a complex compound was prepared. [Example 1-1 and Examples 3-1 to 7-1]
탄닌산 수용액 대신 갈산 수용액을 사용한 것을 제외하고는, 상기 실시예 1 및 실시예 3 내지 7과 동일하게 진행하였다.  The same procedure as in Example 1 and Examples 3 to 7 was performed except that an aqueous solution of gallic acid was used instead of an aqueous solution of tannic acid.
<실험예 > Experimental Example
치아시편에 조성물 도포  Applying Composition to Dental Specimen
준비된 치아 시편을 상기 실시예의 조성물에 약 1분 간 침지하였으며, 침지 후, 꺼내어 증류수로 세척하였다. 침지 몇 세척을 4회 반복하여 시행하였다. 치아표면의 관찰  The prepared tooth specimen was immersed in the composition of the above Example for about 1 minute, after immersion, taken out and washed with distilled water. Several immersion washes were repeated four times. Observation of the tooth surface
조성물이 도포된 치아 시편에 대해 구강 내와 유사한 환경을 적용하기 위해 인공 타액을 준비하였다.  Artificial saliva was prepared to apply an environment similar to the oral cavity on the tooth specimen to which the composition was applied.
50mM의 Tris 완충 용액에 염화칼슘 (CaCl2), 인산포타슘 (potassium phosphate, K2HP04), 불소나트륨 (NaF) 및 염화나트륨 (NaCl)의 염을 각각 다음과 같은 농도가 되도록 첨가하였다. To a 50 mM Tris buffer solution, salts of calcium chloride (CaCl 2 ), potassium phosphate (potassium phosphate, K 2 HP0 4 ), sodium fluoride (NaF) and sodium chloride (NaCl) were added to the following concentrations, respectively.
염화칼슘 2.58mM, 인산포타슴 1.55mM, 불소나트륨 lmg/L, 및 염화나트륨 Calcium Chloride 2.58mM, Potassium Phosphate 1.55mM, Sodium Fluoride lmg / L, and Sodium Chloride
180mM. 180mM.
여기에 0.1M의 염산 수용액을 점적하여 pH가 7.6이 되도록 조절하여 인공 타액을 준비하였다.  0.1M hydrochloric acid aqueous solution was added dropwise to adjust the pH to 7.6 to prepare artificial saliva.
위에 준비된 인공 타액에, 조성물 도포 처리된 치아 시편을 침지하고, 회전식 인큐베이터에 넣어 37°C , lOOrpm의 속도로 조절하여 일주일 간 보관하였다. 보관 기관 동안에 인공 타액은 약 24시간을 주기로 새로이 갈아주었다. 7일 후 시편올 꺼내어, 증류수로 세척하고， 그 중 일부를 채취하여， SEM을 이용하여 그 표면 및 단면을 관찰하였다. To the artificial saliva prepared above, the tooth composition treated with the composition was immersed, put in a rotary incubator and stored at a rate of 37 ° C, 100 rpm for a week. During storage, artificial saliva was refreshed every 24 hours. After 7 days, the specimens were taken out, washed with distilled water, some of them were collected, and the surface and the cross section thereof were observed by SEM.
도 3은 상기 실시예 1의 조성물이 처리된 치아 시편 표면에 대해 관찰한 SEM 이미지이다.  3 is an SEM image observed on the surface of the dental specimen treated with the composition of Example 1.
도 3을 참조하면, 시편의 표면에 상아세관이 거의 관찰되지 않는 것을 확인할 수 있다. 도 1과 비교해볼 때, 표면의 상아세관이 본 조성물로 인한 코팅 층의 형성 및 하이드록시아파타이트 층의 형성으로 거의 밀봉된 것을 확인할 수 있다ᅳ Referring to Figure 3, it can be seen that almost no ivory tubules observed on the surface of the specimen. Compared with FIG. 1, it can be seen that the surface of the ivory tubule is almost sealed by the formation of the coating layer and the formation of the hydroxyapatite layer due to the present composition. There is
도 4는 상기 실시예 1의 조성물이 처리된 치아 시편의 다양한 단면을 관찰한 SEM 이미지이다.  FIG. 4 is an SEM image of various cross sections of the dental specimen to which the composition of Example 1 is treated. FIG.
도 4를 참조하면, 시편의 표면 등에 코팅 충이 형성되어, 균일한 높이를 형성하는 것을 확인할 수 있으며, 특히 도 2에서 관찰되었던， 치아 손상 등으로 인한 울통불통한 요철이 사라진 것을 확인할 수 있다 (우 상). 또한, 도 4의 아래 두 이미지를 참조하면, 치아의 표면에 덩어리가 형성된 것을 확인할 수 있는데, 이는 탄닌산-철 (III) 착화합물의 코팅 층 상에 인공타액의 칼슘 및 인 성분이 침착되어 하이드록시아파타이트 층이 형성된 것으로 확인할 수 있다.  Referring to Figure 4, it can be seen that the coating filling is formed on the surface of the specimen, to form a uniform height, in particular, as observed in Figure 2, it can be seen that the uneven irregularities due to tooth damage, etc. disappeared (right Prize). In addition, referring to the following two images of FIG. 4, it can be seen that a lump is formed on the surface of the tooth, which is formed of hydroxyapatite by depositing calcium and phosphorus components of artificial saliva on the coating layer of the tannin-iron (III) complex. It can be confirmed that a layer is formed.
도 5는 상기 실시예 1의 조성물 처리 전 후, 치아 시편 표면의 상아세관에 대해 관찰한 SEM 이미지이다.  FIG. 5 is an SEM image of the dentin tubular surface of the dental specimen surface before and after treatment with the composition of Example 1. FIG.
도 5를 참조하면, 조성물 처리 전 관찰되었던 상아세관 (좌)이 본 조성물의 처치로 인해 밀봉된 것 (우)올 명확히 확인할 수 있다.  Referring to FIG. 5, it can be clearly seen that the ivory tubules (left) observed prior to treatment of the composition are sealed (right) due to the treatment of the present composition.
도 7은 실시예 1의 조성물 처리 후, 상기 치아 시편의 표면에 대한 EDX 스펙트럼을 나타낸 것이다.  7 shows the EDX spectrum of the surface of the dental specimen after treatment of the composition of Example 1. FIG.
도 7을 참조하면， 조성물 도포 직후 (좌)와 도포 7일 후 (우)를 비교할 때， 치아 시편 표면에서， 칼슘 및 인의 함량이 크게 증가한 것을 확인할 수 있다. 칼슘 및 인은 하이드록시아파타이 의 주 성분으로, 칼슘 및 인의 함량이 크게 증가한 것은 탄닌산-철 (III) 착화합물의 코팅 층 상에 인공 타액의 칼슴 및 인 성분이 침착되어 하이드록시아파타이트 층이 효과적으로 형성된 것으로 해석할 수 있으며, 이로 인해 치아의 손상된 부분이 재생된 것으로 해석할 수 있다. 또한, 상기 실시예 1 및 실시예 1-1의 조성물 처리 후, 생성된  Referring to FIG. 7, when comparing the composition immediately after application of the composition (left) and after 7 days of application (right), it can be seen that the content of calcium and phosphorus increased significantly on the surface of the tooth specimen. Calcium and phosphorus are the main constituents of hydroxyapatite, and the large increase in the calcium and phosphorus content is due to the deposition of the artificial saliva and phosphorus components on the coating layer of tannin-iron (III) complex, effectively forming the hydroxyapatite layer. It can be interpreted that the damaged part of the tooth is reproduced because of this. In addition, after the composition treatment of Example 1 and Example 1-1,
하이드톡시아파타이트 층올， 별도로 수집하여, 일반 치아 시편과 그 성분 비교를 위해 EDX 스펙트럼을 측정하였다. Hydroxyapatite layerols, collected separately, were measured for EDX spectra for comparison with normal dental specimens and their components.
도 8은 실시예 1 및 실시예 1-1의 조성물 처리 후， 생성된  8 is produced after the composition treatment of Example 1 and Example 1-1
하이드톡시아파타이트 층에 대한 EDX 스펙트럼을 나타낸 것이다. EDX spectra for the hydroxyapatite layer are shown.
도 8을 참조하면, 상기 실시예 1 및 실시예 1-1의 조성물 처리 후, 생성된 하이드록시아파타이트은, 일반 치아 시편과 비교하였을 때, Ca/P의 비율이 유사한 것을 확인할 수 있으며, 이로부터 본 발명의 조성물 처리 후， 생성된  Referring to Figure 8, after the composition treatment of Example 1 and Example 1-1, the resulting hydroxyapatite, when compared to the general dental specimens, it can be seen that the ratio of Ca / P is similar, as seen from this After treatment with the composition of the invention,
하이드록시아파타이트 층이， 일반적인 치아와 유사한 조성을 가지고 있음을 확인할 수 있다. The hydroxyapatite layer has a composition similar to that of regular teeth. You can check it.
도 9 내지 도 1 1은 실시예 1, 3 내지 7, 1-1， 및 3-1 내지 7-1의 조성물 처리 전 후， 치아 시편 표면의 상아세관 정면 및 단면에 대해 관찰한 SEM 이미지이다. 도 9 내지 11을 참조하면, 조성물 처리 전의 치아시편과 도포 후를 비교할 때, 치아 표면의 상아세관이 효과적으로 봉쇄된 것을 확인할 수 있으며, 특히 도포 7일 후에는, 표면에 덩어리가 형성되어, 노출되어있던 상아세관의 표면뿐 아니라, 상아세관 내부 역시 봉쇄된 것올 확인할 수 있는데, 이로부터 상술한 착화합물의 코팅 층 상에 인공타액의 칼슴 및 인 성분이 침착되어  9 to 1 are SEM images observed on the front and cross section of the ivory tubule on the surface of the tooth specimen before and after treatment with the compositions of Examples 1, 3 to 7, 1-1, and 3-1 to 7-1. 9 to 11, when comparing the tooth specimen before the composition treatment and after application, it can be seen that the dentinal tubules on the tooth surface effectively blocked, especially after 7 days of application, a lump is formed on the surface, exposed In addition to the surface of the ivory tubules, the interior of the ivory tubules can be confirmed that the blockage, from which the scab and phosphorus components of artificial saliva are deposited on the coating layer of the complex
하이드록시아파타이트 층이 형성된 것을 알 수 있다. 내구성 확인 실험 It can be seen that the hydroxyapatite layer is formed. Durability Check Experiment
상기 실시예 1의 조성물이 처리되어 탄닌산-철 (III) 착화합물의 코팅 층 상에 하이드톡시아파타이트 층이 형성된 치아 시편올 직경 약 10mm, 두께 약 lmm의 디스크 형태로 준비하였다.  The composition of Example 1 was treated to prepare a dental specimen having a hydroxyapatite layer on the coating layer of the tannic acid-iron (III) complex, which had a diameter of about 10 mm and a thickness of about l mm.
상기 치아 시편에 대해 ISO 11609에 부합하는 장비를 이용하여, 150g의 하중으로 100회의 잇솔질올 실시하였다. 잇솔질이 완료된 시편의 표면을  The tooth specimens were subjected to 100 times brushing with a load of 150 g using equipment in accordance with ISO 11609. The surface of the specimen
SEM으로 관찰하였다. Observed by SEM.
도 12는 잇솔질 완료 후 치아 시편의 표면을 관찰한 SEM 이미자이다. 도 12를 참조하면， 잇솔질 후에도 상아세관이 거의 노출되지 않은 것을 확인할 수 있다. 즉， 본원의 조성물에 의한 탄닌산-철 (III) 착화합물의 코팅 층 및 그 위에 형성된 하이드록시아파타이트 층은, 일반적인 구강 환경 조건에서 잇솔질에 의해서도 탈락하지 않은 것을 확인할 수 있었으며, 이에 따라 본원의 조성물이 시린이 치료용으로 사용될 경우, 내구성이 측면에서 매우 우수한 것을 확인할 수 있었다. 변색 평가실험  12 is an SEM image of the surface of the tooth specimen after brushing. Referring to FIG. 12, it can be seen that even after brushing, the ivory tubules are hardly exposed. That is, the coating layer and the hydroxyapatite layer formed thereon of the tannin-iron (III) complex compound according to the composition of the present application was confirmed that it did not drop off even by brushing under normal oral environmental conditions, and thus the composition of the present application When used for this treatment, it was confirmed that the durability is very excellent in terms of. Discoloration evaluation experiment
상기 실시예 3 내지 7에 따른 구강 도포용 조성물 처리 전, 후의 치아 시편에 대하여, Lab 색 지수를 측정하였으며, 하기 수학식 1 내지 3에 따라 계산되는 색상 지수 변화 (ΔΕ) 및 미백 지수 변화 (AW*)로, 변색 여부를 평가하여， 하기 표 1에 정리하였다. 1]
Figure imgf000023_0001
Lab color index was measured for the dental specimens before and after treatment with the composition for oral application according to Examples 3 to 7, color index change (ΔΕ) and whitening index change (AW) calculated according to Equations 1 to 3 below. *), The color change was evaluated and summarized in Table 1 below. One]
Figure imgf000023_0001
[수학식 2]
Figure imgf000023_0002
[Equation 2]
Figure imgf000023_0002
[수학식 3] [Equation 3]
ᅀ W* = W* ( af ter )ᅳ * (bef ore ) * W * = W * (af ter) ᅳ * (bef ore)
【표 1】  Table 1
Figure imgf000023_0003
상기 표 ί을 참조하면, 상기 실시예 3 내지 7의 경우, 구강 내, 치아 표면에 도포하더라도, 색상 변화 값이 크지 않은 것을 확인할 수 있다.
Figure imgf000023_0003
Referring to Table ί, it can be seen that in Examples 3 to 7, even if applied to the oral cavity, the tooth surface, the color change value is not large.
ΔΕ 값의 경우,모든 실시예에서 약 3 내지 약 25 범위로, 색상 변화가 심하지 않은 것을 확인할 수 있으며, 특히, 실시예 4 내지 6의 경우, 색상지수 ΔΕ 값이 약 3 내지 약 6의 범위에 위치하기 때문에, 치아의 색상 변화를 육안으로 쉽게 식별하기 어려울 정도로, 색상 변화가 심하지 않은 것을 확인할 수 있다. AW* 값의 경우 역시, 모든 실시예에서 약 -20 내지 약 20의 범위로， 색상 변화가 심하지 않은 것을 확인할 수 있으며, 특히 실시예 3 내지 실시예 6의 경우 W* 값이 양의 값을 가지게 되어, 본 발명의 조성물 도포에 의해 치아 미백 효과 역시 기대할 수 있음을 확인할 수 있다. In the case of the ΔΕ value, it can be seen that the color change is not severe in the range of about 3 to about 25 in all embodiments, and in particular, in Examples 4 to 6, the color index ΔΕ value is in the range of about 3 to about 6 Because of the location, it can be seen that the color change is not so severe that it is difficult for the naked eye to easily identify the color change. In the case of the AW * value, too, in all the ranges of about -20 to about 20, it can be seen that the color change is not severe, especially in the case of Examples 3 to 6 W * value to have a positive value It can be seen that the tooth whitening effect can also be expected by applying the composition of the present invention.

Claims

【특허청구범위】 【Patent Claims】
【청구항 11 【Claim 11
탄닌산 (tannic acid) 및 갈산 (gallic acid)을 포함하는 군에서 선택된 1종 이상의 루이스 염기; 및 At least one Lewis base selected from the group containing tannic acid and gallic acid; and
철 (II) 이온, 철 (III) 이온, 스트론튬 (III) 이온， 칼슘 (II) 이온, 이산화티타늄 (Ti02), 산화 철 (Fe203), 수산화 철 (Fe(OH)2), 산화 칼슘 (CaO), 수산화 칼슘 (Ca(OH)2), Iron (II) ion, iron (III) ion, strontium (III) ion, calcium (II) ion, titanium dioxide (Ti0 2 ), iron oxide (Fe 2 0 3 ), iron hydroxide (Fe(OH) 2 ), Calcium oxide (CaO), calcium hydroxide (Ca(OH) 2 ),
실리콘 (Si), 및 실리카 (Si02)를 포함하는 군에서 선택된 1종 이상의 루이스 산을 포함하는, 구강 도포용 조성물. A composition for oral application comprising at least one Lewis acid selected from the group consisting of silicon (Si) and silica (SiO 2 ).
【청구항 2] [Claim 2]
계 1항에 있어서, In clause 1,
상기 루이스 염기 및 상기 루이스 산 중 적어도 일부는 루이스 산에 루이스 염기가 배위된 착화합물 형태로 존재하는， 구강 도포용 조성물. A composition for oral application, wherein at least some of the Lewis base and the Lewis acid exist in the form of a complex in which the Lewis base is coordinated with the Lewis acid.
【청구항 3 ] [Claim 3]
겨 12항에 있어서, In paragraph 12,
상기 착화합물은 2배위 착화합물， 4배위 착화합물, 및 6배위 착화합물로 이루어진 군에서 선택된 1종 이상을 포함하^, 구강 도포용 조성물. The complex compound includes at least one selected from the group consisting of a 2-coordinate complex, a 4-coordinate complex, and a 6-coordinate complex, and a composition for oral application.
【청구항 4】 【Claim 4】
제 1항에 있어서, According to clause 1,
상기 루이스 염기 및 상기 루이스 산을 각각 O.Olmg/ml 내지 lmg/ml 농도로 포함하는, 구강 도포용 조성물. A composition for oral application comprising the Lewis base and the Lewis acid at a concentration of 0.0 mg/ml to 1 mg/ml, respectively.
【청구항 5】 【Claim 5】
제 1항에 있어서, According to clause 1,
상기 루이스 염기 및 루이스 산을 으 5:1 내지 10:1의 몰 비율로 포함하는, 구강 도포용조성물. A composition for oral application comprising the Lewis base and Lewis acid at a molar ratio of 5:1 to 10:1.
【청구항 6】 제 1항에 있어서, 【Claim 6】 According to clause 1,
' pH가 3 내지 8 범위인, 구강 도포용 조성물. 'A composition for oral application having a pH in the range of 3 to 8.
【청구항 7] [Claim 7]
제 1항에 있어서， In clause 1,
별도의 실리카 입자를 더 포함하는, 구강 도포용 조성물. A composition for oral application, further comprising separate silica particles.
【청구항 8】 【Claim 8】
거 V7항에 있어서, In clause V7,
상기 실리카 입자는, 수평균 입경이 0.05 내지 5 인, 구강 도포용 조성물. The composition for oral application, wherein the silica particles have a number average particle diameter of 0.05 to 5.
【청구항 9】 【Claim 9】
. 제 1항에 있어서, . According to clause 1,
용액, 페이스트, 에어로졸， 또는 레진 형태의 제형을 갖는, 구강 도포용 조성물. A composition for oral application having a formulation in the form of a solution, paste, aerosol, or resin.
【청구항 10] [Claim 10]
탄닌산 (tannic acid) 및 갈산 (gallic acid)을 포함하는 군에서 선택된 1종 이상의 루이스 염기; 및 At least one Lewis base selected from the group containing tannic acid and gallic acid; and
철 (Π) 이온, 철 (III) 이온, 스트론튬 (III) 이온， 칼슘 (II) 이온, 이산화티타늄 (Ti02): 산화 철 (Fe203), 수산화 철 (Fe(OH)2), 산화 칼슘 (CaO), 수산화 칼슴 (Ca(OH)2), Iron (Π) ion, iron (III) ion, strontium (III) ion, calcium (II) ion, titanium dioxide (Ti0 2 ) : iron oxide (Fe 2 0 3 ), iron hydroxide (Fe(OH) 2 ), Calcium oxide (CaO), calcium hydroxide (Ca(OH) 2 ),
실리콘 (Si), 및 실리카 (Si02)를 포함하는 군에서 선택된 1종 이상의 루이스 산;을 반웅시키는 단계를 포함하는 구강 도포용 조성물의 제조 방법. A method for producing a composition for oral application comprising the step of reacting at least one Lewis acid selected from the group consisting of silicon (Si) and silica (SiO 2 ).
【청구항 1 1 1 【Claim 1 1 1
제 10항에 있어서， In clause 10,
상기 루이스 염기 및 상기 루이스 산의 착화합물을 형성하는 단계를 Forming a complex of the Lewis base and the Lewis acid
포함하는, 구강 도포용 조성물의 제조 방법. A method for producing a composition for oral application, comprising:
【청구항 12】 제 10항에 있어서， 【Claim 12】 In clause 10,
상기 루이스 염기 및 루이스 산을 0.5: 1 내지 10: 1의 몰 비율로 반웅시키는 구강 도포용 조성물의 제조 방법. A method for producing a composition for oral application in which the Lewis base and Lewis acid are reacted at a molar ratio of 0.5: 1 to 10: 1.
【청구항 13 ] [Claim 13]
제 10항에 있어서， In clause 10,
상기 반응시키는 단계는 pH가 3 내지 8 범위에서 수행되는 구강 도포용 조성물의 제조 방법. The reaction step is a method of producing a composition for oral application wherein the pH is in the range of 3 to 8.
【청구항 14] [Claim 14]
제 10항에 있어서， In clause 10,
상기 반웅시키는 단계는 4 내지 6( C의 온도 범위 및 으 1 내지 5atm의 압력 범위 하에서 수행되는 구강 도포용 조성물의 제조 방법. The reaction step is a method of producing a composition for oral application, wherein the reaction is performed under a temperature range of 4 to 6 C and a pressure range of 1 to 5 atm.
【청구항 15】 【Claim 15】
제 10항에 있어서, According to clause 10,
상기 루이스 염기 및 상기 루이스 산의 착화합물로, 실리카 입자를 코팅하는 단계를 더 포함하는， 구강 도포용 조성물의 제조 방법. A method for producing a composition for oral application, further comprising coating silica particles with a complex of the Lewis base and the Lewis acid.
【청구항 16】 【Claim 16】
제 1항에 따른 구강 도포용 조성물을 상아세관이 노출된 구강 내부에 도포하여 코팅층을 형성하는 단계를 포함하는, 상아세관 밀봉 방법. A dentinal tubule sealing method comprising forming a coating layer by applying the oral composition according to claim 1 to the inside of the oral cavity where the dentinal tubules are exposed.
【청구항 17】 【Claim 17】
제 16항에 있어서, According to clause 16,
상기 코팅층 상에, 하이드록시아파타이트 층을 형성하는 단계를 포함하는, 상아세관 밀봉 방법. A dentinal tubule sealing method comprising forming a hydroxyapatite layer on the coating layer.
PCT/KR2015/004343 2014-04-29 2015-04-29 Composition for oral application and method for preparing same WO2015167257A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US15/307,800 US20170049669A1 (en) 2014-04-29 2015-04-29 A composition for oral application and a method for preparing the same

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2014-0051815 2014-04-29
KR20140051815 2014-04-29
KR1020150059920A KR20150124919A (en) 2014-04-29 2015-04-28 Oral composition and method for preparing thereof
KR10-2015-0059920 2015-04-28

Publications (1)

Publication Number Publication Date
WO2015167257A1 true WO2015167257A1 (en) 2015-11-05

Family

ID=54358899

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2015/004343 WO2015167257A1 (en) 2014-04-29 2015-04-29 Composition for oral application and method for preparing same

Country Status (1)

Country Link
WO (1) WO2015167257A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2805526C2 (en) * 2022-02-22 2023-10-18 Общество С Ограниченной Ответственностью "Сплат Глобал" Synergetic remineralizing combination

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999004764A1 (en) * 1997-07-23 1999-02-04 Perio Products Ltd. Tannic acid-polymer compositions for controlled release of pharmaceutical agents, particularly in the oral cavity

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999004764A1 (en) * 1997-07-23 1999-02-04 Perio Products Ltd. Tannic acid-polymer compositions for controlled release of pharmaceutical agents, particularly in the oral cavity

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
A. T. IFFAT ET AL.: "Study of Complex Formation of Fe(III) with Tannic Acid", J. CHEM. SOC. PAK, vol. 27, no. 2, 2005, pages 174 - 177, XP055234649 *
HIROTAKA EJIMA ET AL.: "One-Step Assembly of Coordination Complexes for Versatile Film and Particle Engineering", SCIENCE, vol. 341, 12 July 2013 (2013-07-12), pages 154 - 157, XP055234642 *
J. A. JAEN ET AL.: "Gallic Acid, Ellagic Acid and Pyrogallol Reaction with Metallic Iron", HYPERFINE INTERACTIONS, vol. 148/149, 2003, pages 227 - 235, XP055234643 *
P. L. DAWSON ET AL.: "Dental Stain Prevention by Abrasive Toothpastes: A new in vitro tes and its correlation with clinical observations", J. COSMET. SCI., vol. 49, 1998, pages 275 - 283, XP055234652 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2805526C2 (en) * 2022-02-22 2023-10-18 Общество С Ограниченной Ответственностью "Сплат Глобал" Synergetic remineralizing combination

Similar Documents

Publication Publication Date Title
TWI363633B (en) Biologically active nanoparticles of a carbonate-substituted hydroxyapatite, process for their preparation and compositions incorporating the same
EP3043868B1 (en) Oral care composition
JP5731459B2 (en) Compositions and methods for preventing or treating conditions or diseases associated with dentin
EP2906182B1 (en) Oral care composition
EA027211B1 (en) Oral care composition
EP3648731B1 (en) Oral care composition
EP3668604B1 (en) Oral care composition
EP3294261B1 (en) Oral care composition
EP3294260B1 (en) Oral care composition
EP3547989B1 (en) Oral care composition
EP3554459B1 (en) Oral care composition
KR20170056499A (en) Oral composition and method for preparing thereof
WO2015167257A1 (en) Composition for oral application and method for preparing same
CN109640928A (en) Oral care composition
JP2023524338A (en) Oral compositions with synergistic association of organic and inorganic ingredients for the maintenance of complete oral health, their manufacturing processes and uses
US20210128610A1 (en) Encapsulated antimicrobials and related methods of treatment
WO2020099068A1 (en) Oral care composition
CN107635534B (en) Oral care compositions
EP3033151B1 (en) Oral care composition
TWI483740B (en) Composition for prophylaxising or treating dentin-associated symptoms or diseases, and mthod using the same
EP3294259B1 (en) Oral care composition
CN110573131B (en) Oral care compositions
WO2023277054A1 (en) Oral composition and method for producing same
El Shahawi et al. Effect of addition of calcium phosphate nanoparticles to bleaching agents on surface hardness and color change of enamel
El Shahawi et al. EFFECT OF ADDITION OF CALCIUM PHOSPHATE NANOPARTICLES TO BLEACHING AGENTS ON SURFACE HARDNESS AND COLOR CHANGE OF ENAMEL. AN IN VITRO STUDY

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15786310

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 15307800

Country of ref document: US

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15786310

Country of ref document: EP

Kind code of ref document: A1