KR20090092520A - One-way fluoride releasing strip for preventing dental caries - Google Patents

Abstract

A one-way fluoride releasing strip for preventing dental caries is provided to suppress washing fluorine away in the strip and prevent dental caries of infants. A fluoride releasing strip for preventing dental caries comprises a support layer and fluorine-containing layer on the support layer. The support layer contains hydrophobic polymer and additionally comprises 20-40 weight part of plasticizer based on the 100 weight part of hydrophobic polymer. The plasticizer is DBP(dibutyl phthalate) or DOP(dioctyl phthalate). The fluorine-containing layer contains drug carrier which is able to seal and release fluorine. The plasticizer is propyleneglycol, glycerin, polyethyleneglycol, caster oil or hydrogenated caster oil.

Description

One-way fluoride releasing strip for preventing dental caries}

The present invention relates to a unidirectional fluorine releasing strip for preventing dental caries and a method of manufacturing the same. More particularly, the present invention includes a support layer and a fluorine-containing layer formed on the support layer. The present invention relates to a fluorine-releasing strip and a method of manufacturing the same, which can prevent dental caries of infants under 3 years old by fluorine release.

Dental caries occurs in the hard tissues of the teeth as a result of mineral deprivation, in which hydroxyapatite is destroyed by acid in the plaque. It is a disease that can be fulfilled once in a person's life, accompanied by toothache and tooth loss, and progresses until the tooth is destroyed. Dental caries can be preventable at the outset and potentially curable.

Among these dental caries, milk caries and multiple caries are specific diseases that occur intensively in infants. Nursing bottle caries are common diseases of the maxillary 4 anterior of infants under 2 years of age and progress very quickly. Infants with this disease often have a habit of sleeping with a bottle of milk in their mouth when they are not breastfeeding.In infants who are breastfed, they are late weaning and often use rubber nipples after soaking in sugar, honey or syrup. Most infants. In the case of rampant caries, a large number of teeth are suddenly rapidly caries and destroyed, and in addition, the teeth are affected by the order in which parts other than the mandibular anterior are erupted in both primary and permanent teeth. It leads. As such, milk caries and multiple caries are very difficult symptoms in terms of repair and prevention.

Infant dental caries is a serious threat to the health of infants, but many infants are at risk due to the lack of parents' perception that child teeth are a substitute and how to deal with caries. Loss of childishness can lead to problems with chewing ability, causing malnutrition, impaired permanent permanent impairment, and problems with space maintenance, which can lead to eruption disorders, and can lead to mental problems of lack of sociality. Therefore, it is very important to prevent premature loss of childish teeth, and in this reality, it is necessary to have a safe and effective approach to preventing dental caries.

Representative methods for preventing dental caries include dental membrane control method, fluorine use method, dental fever coloration method, diet control method. Among them, in 1938, Dean started research on the inverse proportion of fluoride ion concentration and caries in drinking water. Fluoride prevents caries from demineralizing hemorrhoids and promoting remineralization. That is, when fluorine ions act on tooth surface enamel and are substituted with hydroxyl groups of enamel hydroxyapatite crystals, it stabilizes apatite crystals and thus prevents dental caries by increasing acid resistance of hemorrhoids. When fluoride is taken during enamel formation, fluorine ion concentration of enamel is increased, which increases acid resistance and suppresses caries. In addition, fluorine coating is developed as an auxiliary means. Fluoride coating method is a method of preventing caries by applying high concentration of fluorine solution to tooth surface after tooth swelling to increase the fluorine ion concentration of enamel. In addition, the topical application of fluoride to more people to find a way to prevent dental caries can be easily applied by oneself without the help of a professional, as a result of the fluoride-containing detergent and fluoride solution brushing method was developed.

However, infants under the age of 3 are very difficult to visit the dentist itself, and the prevention is not well done because it depends a lot on the recognition of the guardian. In addition, it is difficult to use a fluoride compounding detergent, or fluorine solution brushing method, which is a method of applying fluorine in the home, because it is difficult to spit out the brushed water, and there is a need to find a more effective method.

First, focus on how to easily supplement fluoride at home to prevent dental caries in children under 3 years of age. Fluoride supplements are used in solution or in solid form and are formulated in tablet form, such as vitamins, so that infants can consume them without any difficulty. In addition, a variety of products are being manufactured and sold that serve as fluoride supplements in addition to foods that are easily consumed by infants such as milk and salt. However, this method also has its limitations. While it can be easily consumed at home, most enamels are formed in the womb, so the idea that fluoride application is more effective than fluoride is used to prevent caries. There must be time for the tooth surface to contact.

Therefore, there is a need for a method of applying fluorine to a model that adheres to a tooth that can be easily done at home, has a safe amount of fluorine, and has time to contact the tooth.

It is an object of the present invention to provide a fluorine-releasing strip containing a fluorine-containing layer which can effectively prevent dental caries by releasing fluorine only in the tooth direction and a method of manufacturing the same.

In order to achieve the above object, the present invention

Support layer; And

It provides a fluorine-emitting strip for preventing dental caries comprising a fluorine-containing layer formed on the support layer.

The invention also

A first step of manufacturing a support layer; And

It provides a method for producing a dental caries prevention fluorine-emitting strip comprising a second step of forming a fluorine-containing layer on the support layer.

According to the present invention, a strip composed of a hydrophobic support layer and a hydrophilic adhesive fluorine-containing layer has different properties of hydrophilicity and hydrophobicity, so that the drug in the strip is unnecessarily washed away by saliva and is only released in one direction toward the teeth. Drug delivery is possible.

In addition, the strip of the present invention can be delivered in a concentrated, relatively high concentration in the teeth than the amount of fluoride intake can effectively prevent dental caries.

1 shows a simplified illustration of a double strip, where (A) is a fluorine-containing layer adhering to a tooth, (B) is a support layer.

Figure 2 shows a scanning electron micrograph of the fluorine-containing layer of the double strip, (a) is 0mg of fluorine-containing strip, experimental group A; (b) is 0.042 mg of fluorine-containing strip (1 × 1 cm ² ), experimental group B; (c) 0.083 mg of fluorine-containing strip (1 × 1 cm ² ), experimental group C; And (d) 0.167 mg of fluorine-containing strip (1 × 1 cm ² ) and experimental group D (× 1,000).

Figure 3 shows the fluorine emission of the strip in PBS solution.

4 shows the fluorine content released from the attachment strip.

FIG. 5 is a graph comparing fluorine content emitted from (a) 0.5 hr, (b) 1 hr, (c) 3 hr, and (d) 5 hr PBS solution and strips of adhesion strips at different time intervals. Strips in PBS solution, stripe bars represent attachment strips.

6 shows the scanning electron micrographs of the normal, demineralized and attached strips (× 5,000 and 10,000), (a) is normal, (b) is demineralized, (c) is experimental group A, and (d) is experimental group B, (e) is experimental group C and (f) is experimental group D.

Figure 7 shows the results of 24, 48 and 72 hours MTT analysis by time zone, in the experimental group EC is the support layer, A, B, C and D is the tooth adhesion layer.

EMBODIMENT OF THE INVENTION Hereinafter, the structure of this invention is demonstrated concretely.

The present invention

Support layer; And

It relates to a fluorine-emitting strip for preventing dental caries comprising a fluorine-containing layer formed on the support layer.

The support layer preferably comprises a hydrophobic polymer that does not release or transmit fluorine.

The hydrophobic polymer is not particularly limited as long as it is a non-toxic, non-irritating and non-sensitizing polymer compound having sufficient flexibility in hydrophobicity to avoid rinsing of the drug by saliva and to release fluorine in only one direction toward the tooth rather than in both directions. More preferably, polyvinylacetate; Alkyl celluloses such as ethyl cellulose and the like; Alkyl (meth) acrylates such as polymethyl methacrylate and the like; Polyvinylpyrrolidone; Polyethylene oxide; Polypropylene oxide; Flonics; Methacryloylethyl betaine / methacrylate copolymer (Yukaformer: manufacturer Mitsubishi, methacryloylethyl betain / methacylate copolymer), methacrylic acid copolymers (methacrylic acid copolymers; Eudragit L 100, Eudragit L 125, Eudragit L 100-55 Methacrylic acid copolymers such as Eudragit L 30D-55), aminoalkylmethacrylate copolymers (Eudragit E 100, Eudragit E 125, Eudragit RL 100, Eudragit RL 30D) and the like; Cellulose acetate phthalate; Or one or more selected from the group consisting of shellac. In addition, any polymeric material that is insoluble in oral conditions between pH 6 and 8, which is used as an enteric coating material, can be used without limitation.

The hydrophobic polymer is preferably included in 1 to 10 parts by weight based on 100 parts by weight of the total composition for preparing the support layer. When the content is less than 1 part by weight, it does not have a tensile strength to withstand as a support layer, for example, it may be torn after casting during the process of making a strip, and when it exceeds 10 parts by weight, toughness increases and flexibility is increased. It can be reduced and detachment from the tooth attachment layer easily occurs, and when applied in the oral cavity, the feeling of foreign body becomes large.

In addition, the support layer may further include 20 to 40 parts by weight of a plasticizer based on 100 parts by weight of the hydrophobic polymer to further improve the physical properties of the polymer. If the content is less than 20 parts by weight, there is a risk that the physical properties of the polymer, such as the ductility of the strip may fall, if more than 40 parts by weight, there is a fear of toxicity.

The plasticizer may be used alone or two or more of DBP (dibutyl phthalate), DOP (dioctyl phthalate) and the like.

In addition, the fluorine-containing layer is

Fluorine; And

It is desirable to include a drug carrier that can encapsulate and release fluorine.

The fluorine content is preferably 0.1 to 0.5 mg of fluorine per 3 × 1 cm ² in consideration of 0.25 mg of fluoride per day safe for infants aged 3 and younger.

In addition, the drug carrier may be used without limitation as long as it is a material capable of encapsulating and releasing fluorine, it is preferable that the drug carrier is a tacky hydrophilic polymer so that the fluorine-containing layer can adhere to the teeth. In addition, when the fluorine-containing layer itself is not tacky, a pressure-sensitive adhesive layer capable of permeation of fluorine may be formed on the fluorine-containing layer.

The hydrophilic polymer plays an important role as a hydrophilic receptor, and is not particularly limited as long as it can be ingested, has good film-forming ability, has sufficient physical strength, and is biodegradable. Preferably, polyalkyl vinyl ether-maleic acid copolymer (PVM / MA copolymer, Gantrez AN 119, AN 139 and S-97), polyvinyl alcohol, polyacrylic acid, Poloxamer407 (Pluronic), polyvinylpyrrolidone-vinylacetate Copolymers (PVP / VA copolymer; Luviskol VA and Plasdone S PVP / VA), polyvinylpyrrolidone (PVP, K-15 to K-120), polyquaternium-11 (Polyquaternium-11, Gafquat 755N), poly Polyquaternium-39 (Polyquaternium-39, Merquatplus 3330), Carbomer (Carbopol), Carbophil, Hydroxyalkylcellulose, Gelatin, such as hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose Alginate such as sodium alginate (sodium alginate) is preferably used alone or two or more.

Preferably, the adhesive polymer is included in an amount of 1 to 10 parts by weight based on 100 parts by weight of the total composition for preparing the fluorine-containing layer. When the content is less than 1 part by weight, the flowability is large, there may be movement during tooth attachment, and when the content is more than 10 parts by weight, the applicability is poor and the fluorine is not evenly distributed in the casting / evaporation process.

In addition, the fluorine-containing layer may further include 15 to 20 parts by weight of a plasticizer based on 100 parts by weight of the hydrophilic polymer to further improve the physical properties of the hydrophilic polymer. When the content is less than 15 parts by weight, there is a risk that the physical properties of the polymer, such as the ductility of the strip may drop, and when more than 20 parts by weight, toxicity may appear.

In addition to propylene glycol, glycerin and polyethylene glycol, the plasticizer may be used alone or in combination of caster oil or hydrogenated caster oil, depending on the solvent used.

Therefore, the strip consisting of the two polymer layers of the present invention has different hydrophilicity and hydrophobicity, so that the drug in the strip is unnecessarily washed away by saliva, and the drug is released in only one direction toward the teeth. . This structure is more concentrated in the teeth than the amount of fluoride intake can be delivered in a relatively high concentration can effectively prevent dental caries.

The invention also

A first step of manufacturing a support layer; And

It relates to a method for producing a dental caries prevention fluorine-releasing strip comprising a second step of forming a fluorine-containing layer on the support layer.

It is preferable to prepare the fluorine emitting strip for preventing dental caries of the present invention using the casting / solvent evaporation technique. More preferably, it is preferable to prepare a double strip by preparing about 5 wt% polymer solution for making the support layer and the fluorine-containing layer, preparing the support layer in the strip mold frame, and preparing the fluorine-containing layer on the completely dried support layer.

The first step is to prepare a polymer solution by mixing 1 to 10 parts by weight of the hydrophobic polymer with respect to 100 parts by weight of solvent and 20 to 40 parts by weight of plasticizer based on 100 parts by weight of the hydrophobic polymer; And

It is preferable to include the step of drying the polymer solution at a temperature condition of 40 to 60 ℃.

The types of the hydrophobic polymer and the plasticizer are as described above.

The second step is to prepare a polymer solution by mixing 1 to 10 parts by weight of the hydrophilic polymer and 15 to 20 parts by weight of a plasticizer and fluorine based on 100 parts by weight of the solvent; And

It is preferable to include the step of drying the polymer solution on the support layer.

The kind of said hydrophilic polymer and its plasticizer is as above-mentioned.

Hereinafter, preferred examples are provided to help understanding of the present invention, but the following examples are merely to illustrate the present invention, and the scope of the present invention is not limited to the following examples.

Example 1 Preparation of Double Strips

(Preparation of solution for preparing support layer and fluorine-containing layer)

Two layered strips were fabricated using the casting / solvent evaporation technique. The support layer containing the plasticizer and the fluorine-containing layer were each made of a 5 wt% polymer solution. First, 5 g of EC (Ethyl cellulose, Sigma chemical Co., No. E-8003, MO, USA) was added to 100 g of EtOH (Ethyl alcohol 99.9%, Duksan Pure Chemical Co. Ltd., South Korea) to make the support layer. After homogeneously mixing for 5 hours, a plasticizer DBP (Dibutyl phthalate 99%, Sigma-Aldrich Chemical Co., MO, USA) was added as much as 30% of the EC polymer and mixed again.

Next, sodium fluoride (Sodium fluoride, Sigma chemical Co., No. S7920, MO, USA) corresponding to each experimental group of Table 1 was dissolved in 100 g of secondary distilled water to make a fluorine-containing layer. 5 g of HPMC ((Hydroxypropyl) methyl cellulose, Sigma Chemical Co., No. H-8384, MO, USA) was dissolved in 100 g of secondary distilled water in which sodium fluoride was dissolved, and mixed homogeneously at 40 ° C for 24 hours. And glycerin (Duksan Pure Chemical Co. Ltd., South Korea) corresponding to 18% (w / w) of the HPMC polymer was added and mixed again. The HPMC solution was stored and used until bubbles were removed.

The experimental group was experimental group A containing no fluorine, experimental group B containing half of fluoride, and experimental group D containing twice of fluorine, based on experimental group C, which is 0.25 mg of fluoride per day, which is safe for infants 2-3 years old to take. Divided. The experiment was designed with strips applied to four anterior teeth of infants, where the average width of the four anterior crowns was approximately 2.3 cm (5.1, 6.5, 6.5, and 5.1 mm, respectively) and the average height was 0.5 cm. The strip to be applied was 3 × 1 cm ² . It was stored in the desiccator until it was used for the experiment.

Composition of the experimental group Experimental group Fluorine content in strips of 3 × 1 cm ² (mg) Sodium fluoride content (mg) in 105 g HPMC solution A 0 0 B 0.125 117 C 0.25 231 D 0.50 465

(Manufacture of Double Strips)

The strip was produced in the following order. 5 ml of EC solution was poured into a 87 mm diameter plastic petri dish (≒ 60 cm ² ) to form a support layer. And dried for 3 hours in a 50 ° C. drying oven [mold area = 59.41 cm ² , volume = 5 ml; Total solids content = 0.25; DBP content for polymer = 30% (w / w); Mixing time of polymer and plasticizer = 5 hours].

5 g of HPMC solution containing fluorine of each experimental group A, B, C, D was poured on the completely dried EC support layer. And completely dried in air for 24 hours [mould weight = 5 g; Total solids content = 0.25 g; Glycerin content for polymers = 18% (mixing time of w / w polymer and plasticizer = 5 hours; fluorine content for 105 g HPMC solution = 0, 117, 231, 465 mg].

A schematic diagram of the completed double strip is shown in FIG.

(Preparation of Teeth Psalms)

After the tooth decay is separated from the jaw bone, the tooth is removed, and the flat part of the enamel is cut into a 1 × 1 cm ² square model using a diamond disc. Enamel tooth specimens were prepared. After embedding the prepared dental specimen in parallel with the bottom of acrylic resin, when the resin is hardened, polish the enamel surface in order from 600 to 800, 1200, 2000 grit (mesh carborundum paper) and finish with the final diamond paste. Ultrasonication was performed for a second. And it was stored at 4 ℃ maintaining 100% humidity until used in the experiment.

(Production of demineralization solution)

In order to form a caries lesion on the enamel surface of the prepared tooth specimen, 2.2 mM CaCl ₂ , 2.2 mM NaH ₂ PO ₄ , and 50 mM acetic acid were mixed in secondary distilled water and adjusted to pH 5.0 to prepare a demineralization solution.

Experimental Example 1 Observation of the Microstructure of the Strip Surface

In order to confirm the microstructure of the surface of a single layer strip containing fluorine from which the EC support layer was removed from the two-layered strip, it was observed at 5,000 and 10,000 times using a scanning electron microscope (SEM; S2700, Hitachi, Japan).

As shown in FIG. 2, the transparency of the strip decreased with increasing fluorine content, but there was no difference in the microstructure of the strip surface according to the fluorine content.

Experimental Example 2 Concentration of Fluorine Emitted from the Double Strip

(Concentration of fluorine released from the strip)

Ionplus fluoride standard 0.1MF ^- hayeoseo diluted (Orion research Inc., No. 940906, MA, USA) took the standard to prepare a solution with 0.019, 0.19, 1.9, 19 ppm . To determine the amount of fluorine released from the strips, each experimental group A, B, C, D strips were immersed in 2 ml of PBS (Phosphate Buffered Saline pH 7.4, Gibco BRL, Invitrogen ^™ , MD, USA). Fluoride ions were measured at 30, 1, 3 and 5 hour intervals. For ion measurement, the above PBS solution and TISAB II (Orion research Inc., No. 940909, MA, USA) were mixed at a ratio of 1: 1 and fluorine ion was obtained using a fluorine ion-selected electrode (Orion Model 720A pH / ISE Meter). The concentration was measured. After fluoride ion measurement, the old PBS was removed and replaced with a new solution.

As shown in FIG. 3, it was confirmed that most of fluorine was released within 1 hour, and fluorine emission thereafter was not confirmed. In experimental groups B, C and D, there was a significant difference in fluorine concentrations measured between 30 minutes and 1 hour (p <0.05) and there was no significant difference between the measured fluoride values released thereafter (p> 0.05).

(Concentration of fluorine released in the attached state)

To measure the concentration of fluorine released into the PBS from the EC support layer with the strip attached to the teeth, the PBS was taken at 30 minutes, 1, 3 and 5 hours after the strip was attached to the dental specimen and immersed in the PBS. The solution and TISAB II were mixed 1: 1 and the concentration of fluorine released was measured.

As shown in Figures 4 and 5, the concentration of fluorine released into the PBS was significantly less than the concentration released in the strip of Figure 3 at each time period (p <0.05). During the fluorine measurement of the strips attached to the teeth, the strips were securely attached for up to 6 hours, spread out from the edges of the strips after 12 hours, and more than half of the strips were suspended in PBS over 24 hours.

Thus, considering the clinical situation from the above results, it is possible to adjust the time for attaching the strip to the indwelling.

In addition, if the infant is attached during bedtime, the flow of saliva is less, the risk of falling of the strip and prevent the infant from rejecting the strip.

Experimental Example 3 Changes in Hardness of Dental Specimen

In order to observe the caries remineralization effect of the strip of the present invention, after forming caries lesions in the caries, they were simulated similarly to the clinical situation. To this end, the dental specimens were demineralized with deliming solution and Vickers hardness was measured to observe the remineralization effect.

(Measurement of Hardness of Normal Teeth Specimen)

Vickers hardness was measured at three points per specimen by applying a static load of 300g for 10 seconds after grading the hardness point on the surface of the normal tooth specimen which was not treated.

(Measurement of hardness after artificial caries formation)

The specimen was immersed in the prepared deliming solution and taken out after 24 hours, and the surface of the dental specimen was dried using compressed air. The Vickers hardness was measured by applying a static load of 300g for 10 seconds while holding the point to measure the hardness in the specimen.

(Measurement of hardness after strip application)

The prepared tooth specimens were randomly picked and divided into five groups. In order to attach the strip to the teeth, immediately after dipping in PBS, the experimental groups A, B, C and D were attached to each. 2 ml of PBS was placed in a plastic conical tube and the stripped teeth were locked. The teeth with the strip attached were left in PBS for 5 hours. And it was stored in the same 37 ℃ water bath in oral conditions. After 5 hours, the dental specimens deposited in PBS were removed to remove the attached strips, and the Vickers hardness was measured at three points per dental specimen. The change in hardness after strip attachment was calculated using the following equation.

Hardness enhancement = VH _A -VH _D / VH _D × 100 (%)

VH _A : Vickers hardness after strip application

VH _D : Vickers hardness after caries lesion

As shown in Table 2, VHN 335.73 ± 43.79 was measured for the Vickers hardness of 300 g for 10 seconds after the preparation of the dental specimen.

The hardness measured after deliming was VHN 34.67 ± 18.80. This value was statistically significant between the two results when compared with the normal tooth specimen (p <0.05).

And randomly divided into five groups for the experiment. There was no significant difference in Vickers hardness between demineralized dental specimens in five randomly divided groups (p> 0.05).

Hardness before and after strip attachment in the same experimental group was significantly increased in the experimental group except for the PBS group (P <0.05).

Therefore, the hardness is improved as described above, it is determined that the strip of the present invention has the effect of remineralization.

Experimental Example 4 Microstructure Analysis of the Surface of the Dental Specimen

After the formation of normal teeth and caries lesions and the application of fluoride release strips, the microstructure of the surface of the tooth was observed at 5,000 and 10,000 times using a scanning electron microscope.

As shown in FIG. 6, the microstructure of the demineralized tooth and the tooth surface before and after application of the strip showed the difference between the demineralized tooth and the remaining tooth surface. In experimental group A, the demineralized needle structure was shortened, and in the remaining experimental groups B, C, and D, the demineralized needle bed was observed as a soft side, but no difference was observed in the experimental group.

In other words, it was observed that the rough boundary of enamel soju was slightly recovered between the demineralized control tooth specimen and the experimental group.

Experimental Example 5 Cytotoxicity Test of Monolayer Strip Using Agar Overlay Test

As the amount of fluorine was important for the safety of infants, the toxicity of each strip was also very important. In the tooth-attached model, agar-layer tests were performed to simulate similar cytotoxicity by simulating the clinical conditions in which fluoride is delivered with enamel layers prior to direct contact with the cells.

Prior to the test, EO gas sterilization was carried out by cutting the test groups A, B, C, and D, which consisted of a slide glass as a negative control, a gutter percha as a positive control, and an EC support layer and a monolayer, to a size of 5 × 5 mm ² .

Rat connective tissue fibroblasts (L-929) were cultured in a medium in which a culture medium and serum were mixed at a ratio of 9: 1. Each Petri dish was evenly mixed with 10 ml of the same medium and rat fibroblasts (L-929) and incubated for 24 hours. After 24 hours, the cells were confirmed to have been cultured in a monolayer at the bottom of the Petri dish and the old medium above was removed. And culture medium: serum: agar on the cells present as a monolayer in a ratio of 4: 1: 5 in a ratio of 10ml each so as not to form a drop and hardened the agar mixture for 10 minutes. When the agar mixture was hardened, 10 ml of diluted neutral red stain solution, which was once filtered, was poured into the cell incubator. After 1 hour, the dye was removed and the test group A, B, C and D specimens of negative control, positive control, EC support layer and monolayer were prepared. 24 hours after the specimen was raised, the areas decolorized and apoptosis were identified under the microscope and evaluated according to the specifications shown in Table 3.

(Statistical analysis)

Statistical processing is performed by SPSS Ver. 12.0 was used and the confidence interval was 95%. Fluoride concentrations released from the double strip, hardness change before and after the formation of caries lesions on the dental specimens, and MTT toxicity assessment were analyzed using One Way ANOVA. Tukey and Duncan were used as post test. Assay was performed.

*: Reaction Index = Bleaching Index / Death Index

As shown in Table 4, in all negative controls, no cell discoloration and death were observed, indicating no cytotoxicity. On the other hand, in all the positive control group, about 5mm of discoloration was observed, which is about 2, and all cells within the discolored range were killed by more than 80%, showing severe cytotoxicity. In the EC corresponding to the support layer, there was a slight discoloration around the material, but there was no apoptosis and no cytotoxicity. In experimental group A, the cytotoxicity was mild due to 5mm discoloration and within 20% of cell death. In B, C, and D, there was about 5mm of discoloration, and as the experimental group D became more severe, the cell was discolored. However, the cell death was about 60%, showing moderate cytotoxicity.

<Experiment 6> Cytotoxicity test of double strip using agar stratification test

The two-layer strip was cut into 5 × 5 mm 2 and sterilized with E.O gas. Sterile slide glass and gutter percha in the same manner as in Experimental Example 5 were used as a negative control and a positive control, respectively. Incubate the cells in a monolayer and pour agar culture solution on it. Specimens were placed so that the EC support layers of the duplicated experimental groups A, B, C and D strips face the agar. Cytotoxicity was evaluated according to Table 3.

As shown in Table 5, in all negative controls, no cell discoloration and death were observed, indicating no cytotoxicity. On the other hand, in all the positive control group, about 10mm of discoloration was observed, which was about 3, and all cells in the discolored range were killed by more than 80%, showing severe cytotoxicity. In the experimental group, the toxicity of the strip through the EC support layer showed mild toxicity in A and B, and moderate toxicity in C and D.

Experimental Example 7 MTT (methylthiazol tetrazolium bromide) analysis

From the results of Experimental Example 6, the range of the reaction index for determining agar cytotoxicity was not presented in detail, and as a result, reduced cytotoxicity in reading the results could not be clearly observed. Therefore, MTT assay was performed on the eluate of the strip to determine cytotoxicity.

Strips from each group were eluted for the MTT test. A strip of 6 cm ² area per ml of RPMI 1640 medium without serum was immersed and eluted at 37 ± 1 ° C. for 24 ± 2 hours of actual clinical conditions.

Cultured rat fibroblasts (L-929) were suspended to 1 × 10 ⁴ cells per 0.18 ml of culture medium, and 0.18 ml were dispensed into each well in 96-well plates. Cells were attached by incubating at 37 ° C. in a 5% CO ₂ incubator for 24 hours, and the eluate was dispensed by 0.02 ml and incubated in the incubator for 24, 48 and 72 hours. Only 0.02 ml of RPMI medium was dispensed as a control. At the end of each incubation, MBS (MTT 3- [4,5-Dimethyl thiazol-2-yl] -2,5-diphenyl-tetrazolium bromide, Sigma-Aldrich Co., No. M2128, MO, USA) reagent Dissolved in MTT solution (5 mg / ml). 0.05ml was added to each well and incubated for 4 hours. Discard the medium and the MTT solution, add 0.05 ml of DMSO (Dimethyl sulfoxide, Amresco ^® Solon Ind.) To each well, shake well so that no crystals remain, and then use a microplate reader (MRX microplate reader, Dynatech, MA, USA). The absorbance of six specimens for each condition in the wavelength range of 570 nm was measured to compare the degree of cytotoxicity with the control.

As shown in FIG. 7, when the toxicity of the control group was 100%, the EC support layer did not show a significant difference. On the other hand, in the experimental group, unlike the agar stratification test, the toxicity was less than 50% of the control group.

It is presumed that the medium was affected by the pH of fluorine in the process of making eluate by stripping the medium, thus affecting cytotoxicity. On the other hand, the support layer did not show a significant difference from the control group using the medium (p <0.05).

Therefore, the strip of the present invention is a fluorine-containing layer showing the cytotoxic toward the teeth, the support layer without the cytotoxicity is exposed in the oral cavity, by releasing a stable amount of fluorine only in the direction of the teeth such as milk bottle caries or multiple caries It can effectively prevent caries. In addition, it can be applied for the purpose of prevention even in the subjects whose behavior is difficult to control.

Claims (18)

Support layer; And A fluorine-emitting strip for preventing dental caries comprising a fluorine-containing layer formed on the support layer. The method of claim 1, A support layer is a fluorine-release strip for preventing dental caries, characterized in that it comprises a hydrophobic polymer. The method of claim 2, Hydrophobic polymers include polyvinylacetate, alkylcellulose, polyalkyl (meth) acrylate, polyvinylpyrrolidone, polyethylene oxide, polypropylene oxide, flonic, (meth) acrylic acid copolymers, cellulose acetate phthalate, and shellac. A fluorine-release strip for preventing dental caries, characterized in that at least one selected from the group consisting of: The method of claim 1, The support layer is a fluorine-emitting strip for preventing dental caries, characterized in that it further comprises 20 to 40 parts by weight of a plasticizer with respect to 100 parts by weight of hydrophobic polymer. The method of claim 4, wherein Plasticizer fluorine releasing strip for dental caries, characterized in that at least one selected from the group consisting of DBP (dibutyl phthalate) and DOP (dioctyl phthalate). The method of claim 1, wherein the fluorine-containing layer Fluorine; And A fluorine releasing strip for preventing dental caries, comprising a drug carrier capable of encapsulating fluorine and releasing it. The method of claim 1, A fluorine-emitting strip for preventing dental caries, characterized in that the fluorine content of the fluorine-containing layer is 0.1 to 0.5 mg per 3 x 1 cm ² . The method of claim 6, A fluorine release strip for preventing dental caries, wherein the drug carrier is a hydrophilic polymer. The method of claim 8, Hydrophilic polymers are HPMC (hydroxypropyl) methyl cellulose, polyalkylvinyl ether-maleic acid copolymer (PVM / MA copolymer), polyvinyl alcohol, polyacrylic acid, Poloxamer407 (Pluronic), polyvinyl pyrrolidone-vinyl acetate copolymer ( PVP / VA copolymer), polyvinylpyrrolidone (PVP), polyquaternium-11, polyquaternium-39, carbomer, carbophyll, hydroxyalkylcellulose, gelatin ( gelatin) and alginate fluorine-release strip for dental caries, characterized in that at least one member selected from the group consisting of. The method of claim 8, A fluorine release strip for preventing dental caries, wherein the drug carrier further comprises 15 to 20 parts by weight of a plasticizer based on 100 parts by weight of a hydrophilic polymer. The method of claim 10, Plasticizer is a fluorine-release strip for preventing dental caries, characterized in that at least one selected from the group consisting of propylene glycol, glycerin, polyethylene glycol, caster oil and hydrogenated caster oil. A first step of manufacturing a support layer; And And a second step of forming a fluorine-containing layer on the support layer. The method of claim 12, The first step is to prepare a polymer solution by mixing 1 to 10 parts by weight of the hydrophobic polymer and 20 to 40 parts by weight of a plasticizer based on 100 parts by weight of the solvent; And Method for producing a dental caries prevention fluorine release strip comprising the step of drying the polymer solution at a temperature condition of 40 to 60 ℃. The method of claim 13, Hydrophobic polymers include polyvinylacetate, alkylcellulose, polyalkyl (meth) acrylate, polyvinylpyrrolidone, polyethylene oxide, polypropylene oxide, flonic, (meth) acrylic acid copolymers, cellulose acetate phthalate, and shellac Method of producing a fluorine-release strip for preventing dental caries, characterized in that at least one selected from the group consisting of. The method of claim 13, Plasticizer is a method for producing a fluorine-release strip for preventing dental caries, characterized in that at least one selected from the group consisting of DBP (dibutyl phthalate) and DOP (dioctyl phthalate). The method of claim 12, The second step is to prepare a polymer solution by mixing 1 to 10 parts by weight of the hydrophilic polymer with respect to 100 parts by weight of solvent and 15 to 20 parts by weight of a plasticizer and fluorine based on 100 parts by weight of the hydrophilic polymer; And Method of producing a fluorine-release strip for preventing dental caries, characterized in that it comprises the step of drying the polymer solution on the support layer. The method of claim 16, Hydrophilic polymers include polyalkylvinyl ether-maleic acid copolymer (PVM / MA copolymer), polyvinyl alcohol, polyacrylic acid, Poloxamer407 (Pluronic), polyvinyl pyrrolidone-vinyl acetate copolymer (PVP / VA copolymer), polyvinylpi From the group consisting of Ralidone (PVP), Polyquaternium-11, Polyquaternium-39, Carbomer, Carbophyll, Hydroxyalkylcellulose, Gelatin and Alginate Method of producing a fluorine-emitting strip for preventing dental caries, characterized in that at least one selected. The method of claim 16, Plasticizer is propylene glycol, glycerin, polyethylene glycol, caster oil (caster oil) and hydrogenated caster oil (hydrogenated caster oil) characterized in that at least one member selected from the group consisting of fluorine-emitting strip for preventing dental caries.