TWI483740B - Composition for prophylaxising or treating dentin-associated symptoms or diseases, and mthod using the same - Google Patents

Description

Composition and method for preventing or treating dentin-related symptoms or diseases

The present invention relates to a preparation for oral teeth, and more particularly to a preparation for preventing or treating a symptom or disease associated with dentin.

Dentin, also known as dentin, is the tissue that forms the main body of the tooth. It is between the enamel and the pulp. Its composition is 70% inorganic, 20% organic, and 10% moisture. Hardness is lower than enamel, but higher than cementum. The dentinal tubule penetrates the entire dentin, and radiates from the surface of the pulp to the enamel. The dentinal tubule is thicker near the end of the pulp, and the thinner the surface, the more branches are separated along the way.

Common dentin-related diseases or symptoms can cause pain, including, for example, dental caries, tooth wearing, enamel loss, or dentin hypersensitivity.

About dentin hypersensitivity, also known as dentin hypersensitivity or sensitive dental dentin, there are many products or methods for relieving dentin hypersensitivity, but none of them have been developed so far. Products or methods provide fast and lasting mitigation.

In general, clinical therapies for dentin hypersensitivity include the following two categories: (1) chemical desensitization methods; and (2) physical desensitization methods.

Regarding the chemical desensitization method, early use of corticosteroids to inhibit the inflammatory response. However, the efficacy of this method is not good.

In addition, protein precipitation, which is a chemical desensitization method, utilizes a chemical agent to coagulate and denature proteins in dentinal tubules. For example, a preparation containing silver nitrate, phenol, formaldehyde or cesium chloride is used to destroy collagen in the dentinal tubule or at the marginal gingiva, thereby forming a sediment block that blocks the opening of the dentinal tubule. However, such preparations can irritate the pulp and gums and have a very high chance of recurrence. Not only that, but silver nitrate also permanently darkens the teeth.

Furthermore, chemical desensitization methods also include the treatment of paralyzed pulpal nerves. For example, commercially available desensitized toothpastes use potassium nitrate to inhibit the ability of the pulp nerve to be intensified. However, according to clinical cases, after two weeks of continuous use of desensitized toothpaste, the patient's pain can be relieved and the effect can only last for several months. In other words, the treatment of paralyzed pulpal nerves does not provide rapid and long-term efficacy, and long-term use of potassium nitrate will also lead to lesions associated with pulpal nerve palsy.

On the other hand, with regard to the physical desensitization method, for example, a dentin tubule sealant is used to directly seal the dentinal tubule opening, wherein the dentin tubule sealant includes, for example, a resin, a glass ionomer (glass ionomer). Cement), or the like. For example, Jensen et al. ("A comparative study of two clinical techniques for treatment of root surface hypersensitivity," Gen. Dent. 35: 128-132.) proposed in 1987 a resin-type dentin adhesive (bonding agent) ) a method of directly closing the dentinal tubules. Although this method can immediately relieve the pain caused by dentin hypersensitivity, it does not provide long-term results. In detail, according to clinical cases, after six months of treatment, the resin-type adhesive will fall off a large amount from the tooth surface. In the case of glass ionomer adhesives, Low et al. ("The treatment of hypersensitive cervical abrasion cavities using ASPA cement," J. Oral Rehabil. 8(1): 81-9.) used glass ionomers to treat teeth in 1981. Essential sensitivity. Although glass ionomers provide efficacy, this material is removed by frequent brushing. In addition, Hansen et al. ("Dentin hypersensitivity treated with a fluoride-containing varnish or a light-cured glass-ionomer liner," Scand. J. Dent. Res. 100(6): 305-9) was reinforced with a resin in 1992. Type glass ionomers are used to treat dentin hypersensitivity, but they also do not provide long-term results.

In summary, how to provide rapid and long-lasting mitigation effects on dentin-related symptoms and diseases remains an important issue to be resolved.

Accordingly, the present invention provides a preparation for oral teeth comprising a calcium ionophore and calcium-containing particles, wherein the calcium-containing particles are carried by the calcium ionophore. Therefore, the preparation for oral cavity of the present invention can prevent or rapidly treat dentin-related symptoms or diseases, and can provide a prolonged preventive or therapeutic effect.

The present invention further provides a method for preventing or treating a symptom or disease associated with dentin, which comprises administering to the oral cavity of an individual the preparation for oral cavity of the present invention.

The present invention further provides a dental treatment method comprising the steps of: providing a composition comprising microparticles comprising calcium particles, calcium and phosphorus containing particles, fluorine-containing particles or a combination thereof; mixing the composition with an acidic solution to form a formulation; and administering the formulation to the oral cavity of the individual.

The present invention also provides a composition for oral care, comprising: a plurality of microparticles, wherein each of the plurality of microparticles has a plurality of pores, and the pore diameter of the pore is between 1 and 100 nm And a calcium-containing component, a phosphorus-containing component, a component containing calcium and phosphorus, a fluorine-containing component, or a combination thereof. Thereby, the composition for oral care of the present invention is advantageous for preventing or rapidly treating dentin-related symptoms or diseases, and can provide a prolonged preventive or therapeutic effect.

The present invention still further provides a method for preventing or treating a symptom or disease associated with dentin, which comprises administering to the oral cavity of the subject the above-described composition for oral care of the present invention.

The present invention still further provides an article comprising the above-described composition for oral care of the present invention, which comprises a dental article, a toothpaste, a dentifrice, an oral cream, a chewing gum, a chewable tablet, a mouth-filled ingot, a mouthwash, a toothbrush or a sticker. sheet.

The embodiments of the present invention are described below by way of specific embodiments, and those skilled in the art can understand the advantages and advantages of the present invention. The present invention may be embodied or applied in various other specific embodiments. The details of the present invention can be variously modified and changed without departing from the spirit and scope of the invention.

In order to solve the conventional problems, after conducting various experiments, the inventors of the present invention have completed a preparation for oral teeth comprising a calcium ion carrier and calcium-containing particles, wherein the calcium-containing particles are composed of the calcium ion carrier Hosted.

The form of the preparation for oral cavity of the present invention is not limited; it is preferably in the form of a gel, a paste, a slurry, an emulsified or a paste.

The calcium ionophore of the present invention is also not limited and may be composed of an organic or inorganic substance. Further, in certain preferred embodiments, the organic material constituting the calcium ionophore may be a polymer, preferably a porous polymer; in some preferred embodiments, the organic substance constituting the calcium ionophore may be an ester. A polymer or an olefinic polymer. For example, preferred ester polymers may include acrylic or polystyrene, and preferred olefinic polymers may include nylon. Further, the calcium ionophore may also be composed of a combination of acrylic, polystyrene and nylon.

Further, regarding the inorganic substance constituting the calcium ion carrier, in some preferred embodiments, the inorganic substance which can be used includes an oxide, and the oxide constituting the calcium ion carrier is not limited, and preferred oxides include, for example, cerium oxide and cerium. Aluminate, titanium dioxide, zinc oxide, aluminum oxide or a combination thereof.

In a preferred embodiment of the formulation for oral care of the present invention, the calcium ionophore of the present invention has a plurality of pores of microparticles. Further, the calcium ion carrier of the present invention is not limited in the manner of carrying calcium particles, and is preferably adsorbed in the pores of the microparticles.

The calcium-containing particles of the present invention are not limited, and are preferably composed of calcium oxide, calcium chloride, calcium carbonate, calcium nitrate, calcium hydride, calcium salts or a combination thereof. In certain preferred embodiments, the calcium-containing particles may comprise phosphorus. Further, the phosphorus-containing calcium-containing particles of the present invention are not limited, and are preferably composed of calcium phosphate, hydroxyapatite, tricalcium phosphate, tetracalcium phosphate, calcium hydrogen phosphate (CaHPO). ₄ ), octacalcium phosphate (Ca ₈ H ₂ (PO4) ₆ ‧5H ₂ O), calcium pyrophosphate (Ca ₂ P ₂ O ₇ ), biomedical glass (Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ ) or a combination thereof.

In a preferred embodiment of the formulation for oral care of the present invention, the pH of the formulation for oral cavity of the present invention is between 2 and 10, preferably between 7 and 10.

The above-described components included in the preparation for the oral cavity of the present invention are merely intended to illustrate the preferred embodiments of the present invention and are not intended to limit the scope of the present invention. That is, the preparation for oral teeth of the present invention may further comprise a calcium ion releasing agent which releases calcium ions from the calcium-containing particles carried by the calcium ion carrier. Specifically, the calcium ion releasing agent of the present invention may be an acidic solution, which is preferably at least one selected from the group consisting of phosphoric acid, oxalic acid, and citric acid, more preferably phosphoric acid. The acidic solution may also be an organic or inorganic acid that is related or similar to any of phosphoric acid, oxalic acid, and citric acid.

In a preferred embodiment of the formulation for oral care of the present invention, the concentration of phosphoric acid is between 1 and 65%, preferably between 25 and 45%, more preferably between 31 and 40. %between.

In another preferred embodiment of the preparation for oral care of the present invention, when the calcium ion releasing agent is an acidic solution, the ratio of the acidic solution to the calcium ion carrier carrying the calcium-containing particles is between 1 and Between 10 mL/g, preferably the ratio of the acidic solution to the calcium ion carrier carrying the calcium-containing particles is between 2 and 5 mL/g.

As noted above, the formulations of the present invention for oral care may or may not include an acidic solution having a pH between 2 and 10. In a particular embodiment, the pH can be between 7 and 10. Further, in the case of including an acidic solution, the pH of the preparation for oral teeth of the present invention may be between 4 and 7, preferably between 5 and 6.

Further, the preparation for oral cavity of the present invention may further comprise other components than the above components. Specifically, the preparation for oral cavity of the present invention may further comprise a fluorine-containing component, and the fluorine-containing component may be a fluorine-containing compound such as a fluoride salt. Preferably, the fluorine-containing component is carried by the calcium ionophore of the present invention described above. In some preferred embodiments, the fluorine-containing component is selected from the group consisting of ammonium fluoride, calcium fluoride, sodium fluoride, potassium fluoride, stannous fluoride, aluminum fluoride, sodium monofluorophosphate, hexafluorophosphate. One of a group consisting of sodium hexafluorosilicate and combinations thereof. Further, the preparation for oral cavity of the present invention may further comprise a pH stabilizer.

In another preferred embodiment of the formulation for oral care of the present invention, the particle size of the microparticles is between 0.1 μm and 100 μm, and the pore size of the pores is between 1 nm and 100 nm. Preferably, the pore size of the pores is between 2 nm and 50 nm.

According to another aspect of the present invention, the present invention provides a method for preventing or treating a symptom or disease associated with dentin, which comprises administering the above-described preparation of the present invention to the oral cavity of an individual. In detail, the dentin-related symptoms which can be prevented or treated by the above method are not limited, and the dentin-related symptoms which can be prevented or treated by the method of the present invention include dentin hypersensitivity, crack tooth syndrome, enamel Enamel loss, loss of dentin, loss of cementum or post-dental sensitivity. Regarding the above-mentioned loss of enamel, loss of dentin or loss of cementum, it is usually caused by erosion, abrasion, abrasion or cracking of the teeth. With regard to the above-mentioned dental post-sensitivity, it usually occurs after dental surgery such as tooth bleaching, patching or complexing.

On the other hand, the disease which can be prevented or treated by the method of the present invention is not limited, and is preferably dental caries, root caries, tooth fracture, root fracture, and tooth neck abrasion ( Cervical abrasion), tooth wearing or dentin-related pulp disease.

According to still another aspect of the present invention, there is provided a dental treatment method comprising the steps of: providing a composition comprising microparticles comprising calcium particles, particles comprising calcium and phosphorus, fluorine-containing particles or a combination thereof; mixing the composition And an acidic solution to form a formulation; and administering the formulation to the oral cavity of the individual.

In a preferred embodiment of the method of dental treatment of the present invention, the microparticles have a plurality of pores having a pore diameter of from 1 to 100 nm, and the calcium-containing particles, the particles containing calcium and phosphorus, the fluorine-containing particles or a combination thereof Adsorbed in the plurality of pores of the microparticles.

In another preferred embodiment of the method of dental treatment of the present invention, the acidic solution is at least one of the group consisting of phosphoric acid, oxalic acid, and citric acid. Preferably, the acidic solution is phosphoric acid, and in this case, the concentration of phosphoric acid may be between 1 and 65%, preferably between 25 and 45%, more preferably between 31 and 40%. between.

In still another preferred embodiment of the method of dental treatment of the present invention, in the step of forming a formulation, the acidic solution is adsorbed with calcium-containing particles, the calcium- and phosphorus-containing particles, the fluorine-containing particles, or a combination thereof. The ratio of the content of the microparticles is between 1 and 10 mL/g. More preferably, in the step of forming the preparation, the ratio of the content of the acidic solution to the particles of the calcium-containing particles, the particles containing calcium and phosphorus, the particles of the fluorine-containing particles or a combination thereof is between 2 and 5 mL. Between /g. Further, in the step of forming the preparation, the formed preparation is preferably in the form of a gel, a paste, a slurry, an emulsified or a paste.

In another preferred embodiment, the method of dental treatment of the present invention comprises administering an aqueous solution to the oral cavity of the individual, and the pH of the aqueous solution is greater than or equal to 7. The aqueous solution to be applied in the method of dental treatment of the present invention is not limited, and it is preferably alkaline water or an alkaline solution prepared in a laboratory. Regarding the above alkaline water, it may be alkaline water obtained from any source, such as commercially available alkaline water or alkaline water prepared in a laboratory, and the pH of the above alkaline water is preferably greater than 7.

In still another preferred embodiment, the method of dental treatment of the present invention further comprises administering water to the oral cavity of the individual. More preferably, water is administered to the oral cavity of the individual prior to administering the alkaline solution to the oral cavity of the individual. Further, the number of times the water is administered to the oral cavity of the individual is not limited, and is preferably at least twice.

According to another aspect of the present invention, the present invention provides a composition for oral care, comprising: a plurality of microparticles, wherein each of the plurality of microparticles has a plurality of pores, and the pore diameter of the pore The system is between 1 and 100 nm; and a calcium-containing component, a phosphorus-containing component, a component containing calcium and phosphorus, a fluorine-containing component or a combination thereof.

In a preferred embodiment of the composition for oral care of the present invention, the calcium-containing component, the phosphorus-containing component, the calcium-and phosphorus-containing component, the fluorine-containing component or a combination thereof of the present invention is adsorbed in the pores of the plurality of microparticles. .

The material constituting the microparticles of the present invention is not limited, and it is preferably composed of an inorganic material or an oxide. By way of example, preferred oxides that can be used to form the microparticles include ceria, yttrium aluminate, titania, zinc oxide, aluminum oxide, or combinations thereof. More preferably, the microparticles of the present invention are composed of cerium oxide.

Regarding the fine particles composed of cerium oxide, the source of the cerium oxide is not limited, and it may be an organic substance containing cerium oxide or an inorganic substance containing cerium oxide. Specifically, the cerium oxide microparticles are preferably formed of ceric acid salt, water glass or tetraalkoxy cerium.

Further, the calcium-containing component of the present invention is not limited, and is preferably selected from the group consisting of calcium oxide, calcium chloride, calcium carbonate, calcium nitrate, calcium hydride, calcium salts, and combinations thereof.

The phosphorus-containing component of the present invention is not limited, and a group consisting of free phosphoric acid, sodium phosphate, potassium phosphate, phosphate, hydrogen phosphate, dihydrogen phosphate, and combinations thereof is preferably selected.

The calcium-containing and phosphorus-containing components of the present invention are not limited, and are preferably selected from the group consisting of free calcium phosphate, hydroxyapatite, tricalcium phosphate, tetracalcium phosphate, calcium hydrogen phosphate, and anhydrous calcium hydrogen phosphate. (CaHPO ₄ ), aqueous calcium hydrogen phosphate (CaHPO ₄ ‧2H ₂ O), octacalcium phosphate and calcium pyrophosphate (Ca ₂ P ₂ O ₇ ) and biomedical glass (Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ ) The group consisting of.

The fluorine-containing component of the present invention is not limited, and it is preferably selected from the group consisting of sodium fluoride or a fluorine-containing compound and a salt, and more preferably sodium fluoride.

In addition, the above-described components included in the composition for oral care of the present invention are merely intended to illustrate the preferred embodiments of the present invention and are not intended to limit the scope of the present invention. That is, the composition for oral care of the present invention may further comprise other components than the above ingredients.

For example, similar to the above-described preparation for oral cavity of the present invention, the composition for oral care of the present invention may further comprise a fluorine-containing component. The fluorine-containing component may be a fluorine-containing compound such as a fluorine salt. Preferably, the fluorine-containing component is selected from the group consisting of ammonium fluoride, calcium fluoride, sodium fluoride, potassium fluoride, stannous fluoride, aluminum fluoride, sodium monofluorophosphate, sodium hexafluoroantimonate (sodium hexafluorophosphate) Sodium hexafluorosilicate) and combinations thereof. Further, the composition for oral care of the present invention may further comprise a pH stabilizer.

In another preferred embodiment of the composition for oral care of the present invention, the pores of the microparticles have a pore size between 2 and 50 nm, and the particle size of the microparticles is between 0.1 μm and 100 μm. .

In another preferred embodiment of the oral care composition of the present invention, the pH of the oral care composition of the present invention is not limited, and the preferred pH may be between 2 and 10, more preferably practical. It is required to be between any of 7 to 10, 4 to 7, or 5 to 6.

Further, the method of producing the composition of the oral care of the present invention is not limited. For example, a microparticle having a plurality of pores can be formed by sequentially using a sol-gel method, and a calcium-containing component, a phosphorus-containing component, a component containing calcium and phosphorus can be formed by impregnation. The fluorine-containing component or a combination thereof is adsorbed in the pores of the microparticles to prepare the oral care composition of the present invention.

According to still another aspect of the present invention, the present invention provides a method for preventing or treating a symptom or disease associated with dentin, which comprises administering the above-described composition of the present invention to the oral cavity of an individual. In detail, the dentin-related symptoms which can be prevented or treated by the method for administering the composition of the present invention are not limited, and preferably include dentin hypersensitivity, crack tooth syndrome, and enamel loss. ), loss of dentin, loss of cementum or post-dental sensitivity. On the other hand, the above-mentioned method for administering the composition of the present invention can prevent or treat a disease without limitation, and preferably includes dental caries, root caries, tooth fracture, root fracture. , cervical abrasion, tooth wearing or dentin-related pulp disease.

According to another aspect of the present invention, there is provided an article comprising the above-described composition of the present invention, which comprises a dental article, a toothpaste, a dentifrice, an oral cream, a chewing gum, a chewable tablet, an ingot, a mouthwash, Toothbrush or patch. Preferably, the dental article of the composition of the present invention may include a dental cement, a dental bonding agent, a dental porcelain powder, and a pulp capping material. ), a retrograde filling material, a root canal filling material, or a composite resin filling material.

In particular, when performing orthodontic treatment, the above-mentioned dental pulp-carrying material can be used for direct or indirect pulpotomy. Further, regarding the apical back filling material, it can be used as a backfill material in a root apical resection.

Example 1: Synthesis of porous microparticles composed of cerium oxide

1 g (g) of gelatin was added to 25 g of deionized water and placed in a constant temperature water bath at 40 ° C for about 15 minutes until completely dissolved to form an aqueous gelatin solution.

Next, 4 g of sodium citrate was dissolved in 100 g of water and placed in a constant temperature water bath at 40 ° C for about 2 minutes to form an aqueous solution of sodium citrate.

On the other hand, about 3.0 mL (ml) of a 6 M sulfuric acid solution was added to 100 g of water and stirred well to prepare an acidic aqueous solution having a pH of about 1. The sodium citrate aqueous solution was mixed with an acidic aqueous solution, and the pH was adjusted to about 5. Next, sodium citrate was aged for 3 minutes, and the above gelatin aqueous solution was further added thereto, and the mixture was stirred in a constant temperature water bath at 40 ° C for about 2 hours until the reaction was completed.

Then, the entire solution (containing the mother liquor) was poured into a water-heated bottle made of PP (polypropene), and placed in a 100 ° C oven for hydrothermal reaction for one day. The obtained product was filtered, washed with water, and dried to obtain a porous cerium oxide material containing gelatin molecules. Finally, calcination was carried out at 600 ° C for 12 hours, and after removing the organic matter, pore-shaped fine particles of cerium oxide were obtained.

Furthermore, by adjusting the pH value of the solution and the number of days of hydrothermal reaction, the pore size of the cerium oxide material can be controlled, and by changing the source of cerium oxide and the weight ratio of gelatin molecules, it is possible to make a difference as needed. Scale microparticles.

Example 2: Preparation of porous microparticles of calcium carbonate-containing cerium oxide

0.09 g of oxalic acid was dissolved in 10 g of deionized water, followed by 0.84 g of calcium carbonate to form a first intermediate solution. Next, 10 g of alcohol was added to the first intermediate solution, and after stirring, 0.5 g of the porous microparticles composed of cerium oxide synthesized in Example 1 was added to form a second intermediate solution.

The second intermediate solution was stirred until dried, placed in an oven, and allowed to stand at 100 ° C for one day. Next, the product taken out of the oven was placed in a high-temperature furnace with air, heated to 200 to 400 ° C, and held at a temperature of 5 hours. Finally, calcium carbonate-containing ceria porous microparticles (hereinafter referred to as Ca-Si based porous particles) are obtained. As shown in Fig. 1, the results of SEM observation of the calcium sulfhydryl-based pore particles of this example are shown.

It is to be understood that the present invention is not intended to limit the scope of the present invention. In other words, in addition to calcium carbonate, the method of the present embodiment can be used to prepare porous microparticles containing other components, such as pore-forming microparticles of calcium phosphate-containing ceria. Further, the preparation method of the porous microparticles of the calcium phosphate-containing ceria is substantially the same as that of the present embodiment, and the main difference is that only the calcium carbonate is substituted with calcium phosphate in the step of forming the first intermediate solution.

Example 3: Preparation of a preparation containing calcium sulfonium-containing pore particles

85.7% of commercially available phosphoric acid (JT BAKER NALYZED, USA) was diluted to a 31% strength phosphoric acid solution with deionized water. 0.05 g of the calcium sulfonium-based porous particles obtained in Example 2 was mixed with 0.15 mL of a 31% strength phosphoric acid solution to prepare a porous microparticle preparation containing calcium carbonate-containing cerium oxide (hereinafter referred to as CaCO ₃ @). Hole SiO ₂ formulation).

Comparative Example 1: Seal & preparation

Commercially available Seal & (Resensitizer, Dentsply DeTrey, Konstanz, Germany) Resin type dentin adhesive. About Seal & It is a light-curing and self-adhesive sealant and is composed of the following components: urethane dimethacrylate resin, polymeric top three Polyrizableizable trimethacrylate resins, dipentaerythritol pentaacrylate phosphate, and amorphous silicon dioxide.

<Test Example 1: Closure effect on dentinal tubules in vitro>

Collect 20 newly-extracted human small molars and large molars, the crown is intact and there is no filling. The calculus and periodontal tissues of the surface of the small molars and the large molars were removed by an ultrasonic washing machine (Sonicflex 2000, Kayo Co Biberbach, Germany). Next, the small molars and large molars were stored in distilled water at 4 ° C to maintain the freshness of the dentin.

Remove the teeth before applying the preparation, use a slow saw blade (Isomet low speed saw, Buehler LTD.,) to remove the occlusal surface enamel of all the teeth in the horizontal direction, and then measure the distance of 1.5 mm along the neck. Next, to obtain a dentin test piece. Next, a groove was formed on the back side of the test piece using a 1960 tapered fissure but to guide the direction in which the test piece was opened in the future. The dentin samples were etched using 37.5% phosphoric acid gel (Gel etchant, Kerr Co USA) for 40 seconds. Then, the smear layer was rinsed with a large amount of distilled water, and the surface of the test piece was blown dry.

The formulation of Example 3 and the Seal & of Comparative Example 1 were used, respectively. The test piece was applied by the following various operation methods: Regarding the CaCO ₃ @ hole SiO ₂ formulation of Example 3, the preparation was applied with a small brush and compacted on the surface of the test piece. After 3 minutes, rinse the surface with water. Next, the above procedure was repeated 3 times, in which the surface agent was rinsed with the alkaline water having a pH of 9 for the third time.

About Seal & Comparative Example 1 , it will be Seal & Apply to the surface of the tooth sample for 20 seconds. Next, blow for 5 seconds and illuminate for 10 seconds. Then, again, Seal & Apply to the surface of the tooth sample. Next, blow for 5 seconds and illuminate for 10 seconds. Complete Seal & Smear.

Finally, the depth of the precipitate in the dentinal tubules of each of the test pieces was observed using a field emission electron microscope (SEM; Field Emission Scanning Electronic Microscope Hitachi S-800, Hitachi Co., Tokyo, Japan).

Fig. 2a and Fig. 2b show the SEM observation results of each group of test pieces, respectively. In detail, Fig. 2a shows the SEM observation results of the dentin test piece coated with the CaCO ₃ @ hole SiO ₂ preparation of Example 3, and Fig. 2b shows the Seal & of Comparative Example 1. SEM observation results of the coated dentin test piece.

After comparison, it can be seen that in the dentinal tubule, the Seal & of Comparative Example 1 The depth of the precipitate provided is only about 10 μm, and there is still a gap between the sediment and the dentinal tubule wall, which does not completely seal the dentinal tubule (see Figure 2b), while the formulation of Example 3 provides a long A sediment depth of about 60 μm and almost 100% closed dentin tubules. In other words, the CaCO ₃ @hole SiO ₂ formulation of Example 3 can provide a better sealing effect for dentin.

<Test Example 2: Permeability test on dentinal tubules in vitro>

The formulation of Example 3 and the Seal & of Comparative Example 1 were evaluated by the flow module test. The penetration of the applied dentin. If the measured permeability is lower, the effect of sealing dentin is better.

The operation of the flow module test is to first provide a glass tube. One end of the glass tube is sealed with a dentin test piece, and the other end of the glass tube is provided with a pressure source of 0.15 g/cm ² and formed in the glass tube. A bubble. After 72 hours, the distance moved by the bubble was measured as a base line. Next, the dentin test piece was applied while the pressure was continuously supplied, and after 72 hours, the bubble moving distance, that is, the penetration distance was measured again. Finally, the reference distance and the penetration distance are substituted into the following equation to calculate the dentin permeability:

Permeability (%) = reference distance / penetration distance × 100%

The procedure for applying the dentin test piece varies depending on the material to be applied.

In detail, regarding the preparation of Example 3, the preparation was applied to the surface of the dentin test piece and pressed to be dense. After 10 minutes, the surface of the dentin test piece was washed with water.

About Seal & Comparative Example 1 , it will be Seal & Apply to the surface of the tooth sample for 20 seconds. Next, blow for 5 seconds and illuminate for 10 seconds. Then, again, Seal & Apply to the surface of the tooth sample. Next, blow for 5 seconds and illuminate for 10 seconds. The results of the above Test Example 3 show that Seal & Comparative Example 1 The dentin test piece exhibited a permeability of about 40%, and the dentin test piece coated with the CaCO ₃ @ hole SiO ₂ formulation of Example 3 exhibited a permeability of about 15%. That is, the CaCO ₃ @porous SiO ₂ formulation of Example 3 of the present invention provides a preferred dentin sealing effect.

<Test Example 3: Closure effect on dentinal tubules in animal experiments>

The dog is anesthetized with a high-speed hand piece for dental use on both sides of the dog, the lower canine and the first large molar side of the buccal tooth. The car is about 5 mm long and wide. A cavity of about 3 mm and a depth of about 1.5 to 2 mm. Next, the coating layer was removed by acid etching with a dental concentration of 37.5% phosphoric acid gel (Gel etchant, Kerr Co. CA, USA) for 40 seconds. Subsequently, the acid on the surface of the tooth is cleaned with a large amount of water to form a sample of the tooth to be filled.

Using the formulations of Example 3 and Comparative Example 1, respectively, the dental samples were filled in the following manner: For the formulation of Example 3, the formulation was applied and compacted to the surface of the tooth sample exposed by the dentin cavity. After 3 minutes, the smeared tooth samples were wiped with a cotton ball dipped in distilled water. Next, the above wiping step was repeated 3 times, in which the third time, a cotton ball having an alkaline water having a pH of 9 was used for wiping. Then, the cavity was filled using a self-polymerizing glass ionomer (GC Fuji II ^TM , GC, Tokyo, Japan).

About Seal & Comparative Example 1 , it will be Seal & Apply to the surface of the tooth sample for 20 seconds. Next, blow for 5 seconds and illuminate for 10 seconds. Then, again, Seal & Apply to the surface of the tooth sample. Next, blow for 5 seconds and illuminate for 10 seconds. Complete Seal & After the application, the cavity was filled with a self-polymerized glass ionomer (GC Fuji II ^TM , GC, Tokyo, Japan).

After one week, the dental samples of each group were removed. Next, the tooth sample was cut open to prepare a test piece. Then, the depth of the precipitate in the dentinal tubules in each of the test pieces was observed using a field emission electron microscope (Field Emission Scanning Electronic Microscope Hitachi S-800, Hitachi Co., Tokyo, Japan).

Figures 3a and 3b show the observations of each set of test pieces, respectively. In detail, Fig. 3a shows the SEM observation results of the dentin test piece of the live dog of the CaCO ₃ @ hole SiO ₂ preparation of Example 3, and the 3b chart shows the Seal & of Comparative Example 1. SEM observation results of the denture test piece of the smeared living dog.

After comparison, it can be seen that in the dentinal tubule, the Seal & of Comparative Example 1 The surface of the dentin is covered with a resin layer, and the resin layer does not closely adhere to the surface of the dentin, and the resin extending into the dentinal tubule is also only about 5 μm (see Fig. 3b), and the preparation of Example 3 A depth of sediment of about 40 μm is provided and the dentinal tubules are almost completely closed (see Figure 3a). In other words, the CaCO ₃ @hole SiO ₂ formulation of Example 3 can provide a better sealing effect for dentin.

<Test Example 4: Evaluation of pulp irritation> The pulp irritation was evaluated in accordance with the specification of the ISO-7405 pulp irritation test.

First, after the dog is anesthetized, the high-speed mobile phone equipped with a spray spray for dental use, on both sides of the dog, the lower canine and the first large molar side of the buccal tooth, the car is about 5 mm long and about 3 mm wide. A cavity about 1.5 to 2 mm deep. Next, the coating layer was removed by acid etching with a dental concentration of 37.5% phosphoric acid gel (Gel etchant, Kerr Co. CA, USA) for 40 seconds. After that, the acid on the surface of the tooth is cleaned with a large amount of water to form a sample of the tooth to be filled.

The formulation of Example 3 and the Seal & of Comparative Example 1 were used. The dental sample was filled by various operations as follows: Regarding the CaCO ₃ @hole SiO ₂ formulation of Example 3, the formulation was applied and compacted on the surface of the tooth sample exposed by the dentin cavity. After 3 minutes, the smeared tooth samples were wiped with a cotton ball dipped in distilled water. Next, the above wiping step was repeated 3 times, in which the third time, a cotton ball having an alkaline water having a pH of 9 was used for wiping. Then, the cavity was filled using a self-polymerizing glass ionomer (GC Fuji IITM, GC, Tokyo, Japan).

About Seal & Comparative Example 1 , it will be Seal & Apply to the surface of the tooth sample for 20 seconds. Next, blow for 5 seconds and illuminate for 10 seconds. Then, again, Seal & Apply to the surface of the tooth sample. Next, blow for 5 seconds and illuminate for 10 seconds. Complete Seal & After the application, the cavity was filled with a self-polymerized glass ionomer (GC Fuji II ^TM , GC, Tokyo, Japan).

Next, on the 7th, 28th, and 70th days, each group of the filled dental samples was taken according to the ISO-7405 pulp irritation test specification to prepare the pulp stimulation test sections. Next, the degree of cell inflammation in the pulp chamber in each group of sections was observed by an optical microscope.

Fig. 4a and Fig. 4b show the results of observation of the degree of cell inflammation in the pulp chamber of each group on the 7th day. In detail, Fig. 4a shows the observation of the pulp tissue pattern of the dentin test piece of the living dog of the CaCO ₃ @ hole SiO ₂ preparation of Example 3, and Fig. 4b shows the Seal & of Comparative Example 1 The observation of the pulp tissue pattern of the smear-coated dentin test piece.

As seen in Figure 4b, Seal & Comparative Example 1 The filled test piece showed a moderate inflammatory response. In detail, it was observed that the cell density in the pulp tissue was increased, the lymphocyte infiltration, and the blood vessel were filled with red blood cells.

In contrast, as can be seen from Fig. 4a, the test piece filled with the CaCO ₃ @ hole SiO ₂ preparation of Example 3 showed no inflammatory or slightly inflamed state. In detail, the pulp tissue has the same appearance as the normal pulp tissue, and there is no inflammatory cell or only a small amount of inflammatory cells in the tissue, and there is no vascular proliferation or erythrocyte oozing out of the blood vessel in the pulp tissue.

From the results of Test Example 4, the CaCO ₃ @ hole SiO ₂ formulation of Example 3 provided a strong anti-inflammatory ability over a long period of time. Thereby, the CaCO3@porous SiO ₂ preparation of Example 3 of the present invention can provide a long-term therapeutic effect.

The above examples are merely illustrative of the compositions and preparation methods of the present invention and are not intended to limit the invention. Modifications and variations of the embodiments described above may be made without departing from the spirit and scope of the invention. Therefore, the scope of the claims of the present invention should be as set forth in the appended claims.

Figure 1 is a view showing the results of SEM observation of the calcium cerium-based porous particles of the examples of the present invention;

Figure 2a shows the SEM observation results of the dentin test piece coated with the CaCO ₃ @ hole SiO ₂ preparation of the embodiment of the present invention;

Figure 2b shows Seal & Comparative Example of the present invention SEM observation results of the coated dentin test piece;

Fig. 3a is a view showing the SEM observation results of the dentin test piece of the living dog coated with the CaCO ₃ @ hole SiO ₂ preparation of the embodiment of the present invention;

Figure 3b shows the Seal & Comparative Example of the present invention SEM observation results of the coated dentin test piece of the living dog;

Figure 4a is a view showing the observation of the pulp tissue type of the dentin test piece of the living dog of the CaCO ₃ @ hole SiO ₂ preparation of the embodiment of the present invention;

Figure 4b shows the Seal & Comparative Example of the present invention The observation of the pulp tissue pattern of the smear-coated dentin test piece.

Claims (53)

A preparation for oral teeth, comprising: a calcium ion carrier, wherein the calcium ion carrier has a plurality of pore microparticles, and the calcium ion carrier is not porous tantalum; calcium-containing particles, wherein the calcium-containing particle system Carrying the calcium ion carrier, and the calcium-containing particles are adsorbed in the pores of the microparticles, and the calcium-containing particles are not phosphate; and the calcium ion releasing agent is the calcium ion carrier from the calcium ion carrier The calcium-containing particles carried are released to form a precipitate in the dentinal tubules, wherein the pH of the preparation is between 2 and 7. The preparation according to claim 1, wherein the calcium ion carrier is composed of at least one organic substance consisting of a group consisting of acrylic, polystyrene, nylon, and a combination thereof. The preparation according to claim 1, wherein the calcium ion carrier is composed of at least one inorganic substance in the group consisting of cerium oxide, cerium aluminate, titanium oxide, zinc oxide, aluminum oxide, and combinations thereof. The preparation according to claim 1, wherein the microparticles have a particle diameter of between 0.1 μm and 100 μm. The preparation of claim 1, wherein the pores have a pore size between 1 nm and 100 nm. The preparation of claim 5, wherein the pore has a pore size between 2 nm and 50 nm. The preparation according to claim 1, wherein the calcium-containing particles are calcium carbonate, calcium chloride, calcium oxide, calcium nitrate, calcium sulfide, calcium Salt or a combination thereof. The preparation according to item 1 of the patent application has a pH of between 4 and 7. The preparation of claim 8, wherein the pH is between 5 and 6. The preparation according to claim 1, wherein the calcium ion release agent is an acidic solution. The preparation according to claim 10, wherein the acidic solution is at least one selected from the group consisting of phosphoric acid, oxalic acid and citric acid. The preparation of claim 11, wherein the acidic solution is phosphoric acid. The preparation of claim 12, wherein the concentration of the phosphoric acid is between 1 and 65 wt%. The preparation of claim 13, wherein the concentration of the phosphoric acid is between 25 and 45 wt%. The preparation of claim 14, wherein the concentration of the phosphoric acid is between 31 and 40% by weight. The preparation of claim 10, wherein the ratio of the volume of the acidic solution to the weight of the calcium ion carrier carrying the calcium-containing particles is between 1 and 10 mL/g. The preparation of claim 16, wherein the ratio of the volume of the acidic solution to the weight of the calcium ion carrier carrying the calcium-containing particles is between 2 and 5 mL/g. The preparation according to claim 1, which is in the form of a gel, a paste, a paste, an emulsion or a paste. The preparation according to item 1 of the patent application includes a fluorine-containing component. The preparation of claim 19, wherein the fluorine-containing component is carried by the calcium ion carrier. The preparation according to claim 19, wherein the fluorine-containing component is selected from the group consisting of ammonium fluoride, calcium fluoride, sodium fluoride, potassium fluoride, stannous fluoride, aluminum fluoride, sodium monofluorophosphate. One of a group consisting of sodium monofluorophosphate, sodium hexafluorosilicate, and combinations thereof. The preparation according to claim 1 of the patent application, further comprising a pH stabilizer. Use of a preparation according to claim 1 of the patent application for the preparation of a medicament for preventing or treating a symptom or disease associated with dentin. The use according to claim 23, wherein the dentin-related symptoms include dentin hypersensitivity, crack tooth syndrome, enamel loss, dentin loss, cementum loss or dentistry Postoperative sensitivity. The use according to claim 23, wherein the dentin-related diseases include dental caries, root caries, tooth fracture, root fracture, and cervical abrasion. ), tooth wearing or dentin-related pulp disease. Use of a preparation for the preparation of a medicament for dental treatment, wherein The formulation is produced by providing a composition comprising microparticles comprising calcium particles, fluorine-containing particles, or a combination thereof, wherein the calcium-containing particles, the fluorine-containing particles, or a combination thereof are adsorbed to the plurality of the microparticles And mixing the composition with an acidic solution to form the formulation, wherein the pH of the formulation is between 2 and 7. The use of claim 26, wherein the microparticles have a plurality of pores having a pore diameter of from 1 to 100 nm. The use according to claim 26, wherein the acidic solution is at least one of the group consisting of phosphoric acid, oxalic acid and citric acid. The use according to claim 28, wherein the acidic solution is phosphoric acid. The use of claim 29, wherein the concentration of the phosphoric acid is between 1 and 65 wt%. The use of claim 30, wherein the concentration of the phosphoric acid is between 25 and 45 wt%. The use of claim 31, wherein the concentration of the phosphoric acid is between 31 and 40% by weight. The use of the invention of claim 26, wherein, in the step of forming the preparation, the volume of the acidic solution is relative to the weight of the microparticles to which the calcium-containing particles, the fluorine-containing particles or a combination thereof are adsorbed The ratio is between 1 and 10 mL/g. The use according to claim 33, wherein in the step of forming the preparation, the volume of the acidic solution is relative to the adsorption of the calcium The ratio of the weight of the particles, the fluorine-containing particles or a combination thereof to the microparticles is between 2 and 5 mL/g. The use according to claim 26, wherein the preparation is in the form of a gel, a paste, a slurry, an emulsified or a paste. The use of claim 26, which comprises applying an aqueous solution to the oral cavity of the individual, and the pH of the aqueous solution is greater than or equal to 7. The use according to claim 36, wherein the aqueous solution is an alkaline water or an alkaline solution. The use of the scope of claim 26 includes the application of water to the oral cavity of the individual. A composition for oral care, comprising: a plurality of micro-particles, wherein each of the plurality of micro-particles has a plurality of pores, and the pore size of the pores is between 1 and 100 nm, and the calcium ion carrier does not Is a porous crucible; a calcium-containing component, a fluorine-containing component or a combination thereof, adsorbed in the pores of the plurality of microparticles, and the calcium-containing component is not a phosphate; and a calcium ion releasing agent which is the calcium ion self The calcium-containing carrier carries the calcium-containing particles to release, so that the calcium ions form a precipitate in the dentinal tubules, wherein the pH of the preparation is between 2 and 7. The composition of claim 39, wherein the pore has a pore size between 2 and 50 nm. The composition of claim 39, wherein the microparticles have a particle size of between 0.1 μm and 100 μm. The composition of claim 39, wherein the pH is between 4 and 7. The composition of claim 42, wherein the pH is between 5 and 6. The composition according to claim 39, wherein the microparticles are composed of at least one inorganic substance in the group consisting of cerium oxide, cerium aluminate, titanium oxide, zinc oxide, aluminum oxide, and combinations thereof. The composition of claim 44, wherein the microparticles composed of cerium oxide are formed of ceric acid salt, water glass, and tetraalkoxy cerium. The composition of claim 39, wherein the calcium-containing component is selected from the group consisting of calcium carbonate, calcium oxide, calcium chloride, calcium nitrate, calcium hydride, calcium salts, and combinations thereof. One. The composition of claim 39, wherein the fluorine-containing component is selected from the group consisting of ammonium fluoride, calcium fluoride, sodium fluoride, potassium fluoride, stannous fluoride, aluminum fluoride, and monofluorophosphate. One of a group consisting of sodium monofluorophosphate, sodium hexafluorosilicate, and combinations thereof. The composition described in claim 39 of the patent application includes a pH stabilizer. Use of a composition according to claim 39 of the patent application for the preparation of a medicament for preventing or treating a symptom or disease associated with dentin. The use according to claim 49, wherein the dentin-related symptoms include dentin hypersensitivity, crack tooth syndrome (crack tooth) Syndrome), enamel loss, loss of dentin, loss of cementum or post-dental sensitivity. The use according to claim 49, wherein the dentin-related diseases include dental caries, root caries, tooth fracture, root fracture, and cervical abrasion. ), tooth wearing or dentin-related pulp disease. An article comprising the composition of claim 39, comprising a dental article, a toothpaste, a dentifrice, an oral cream, a chewing gum, a chewable tablet, a mouthwash, a mouthwash, a toothbrush or a patch. The article of claim 52, wherein the dental article comprises a hormone, a dental adhesive, a dental porcelain powder, a pulp core material, a root tip backfill material, a root canal filling material or a composite resin Fill the material.