Tooth surface coloring composition

Riboflavin 5-sodium phosphate-based tooth surface coloring composition allows safe and aesthetic observation of bacterial films and acquired coats, addressing the limitations of conventional staining methods by enhancing dental hygiene through precise visualization.

JP7618149B2Active Publication Date: 2025-01-21AIOBIO CO LTD +1
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Patent Information

Application Number
JP2023562444
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2020-12-21
Filing Date
2021-12-21
Publication Date
2025-01-21
Estimated Expiration
2041-12-21

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Abstract

Regarding a tooth surface coloring composition and a tooth surface coloring agent containing the same, the tooth surface coloring composition of the present invention can not only color (stain) the tooth surface bacterial film (biofilm), but also the planned formation site of the tooth surface bacterial film, i.e., the acquired film, and by analyzing the color and intensity of the fluorescence emitted by the riboflavin 5-phosphate sodium of the present invention, various information regarding the amount and properties of the tooth surface bacterial film can be obtained, and it is expected that the composition can be usefully used in observing the initial stage of the tooth surface bacterial film.
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Description

[Technical field]

[0001] The present invention relates to a tooth surface coloring composition, and more particularly to a tooth surface coloring composition containing sodium riboflavin 5-phosphate. [Background technology]

[0002] Generally, a large amount of bacteria constantly enters the human oral cavity through food, and the oral cavity is kept in a hot and humid condition, making it easy for bacteria to multiply.

[0003] Oral bacteria destroy the tissue surrounding the teeth by breaking down carbohydrates, such as sugars and starches, in food. These bacteria attach persistently to the tooth surface and form a colorless film, called the dental bacterial film.

[0004] Such tooth surface bacterial film gradually grows larger due to the proliferation of new and existing bacteria and the accumulation of metabolic substances of bacteria and the host, and is the main cause of tooth decay, cold tooth decay, bad breath, and periodontal disease. This can only be removed by physical methods such as brushing the teeth, without being removed by the self-cleaning action of the oral cavity, i.e., saliva. If brushing the teeth is neglected, the bacteria are not clearly removed and remain between the gums and teeth or between the teeth, and over time the bacteria attach to the teeth and the tooth surface bacterial film is formed again.

[0005] Meanwhile, the bacterial film on the tooth surface may be formed as a thin film called a tooth surface thin film or an acquired film on the tooth surface. Currently, a method for checking the bacterial film on the tooth surface using an optical device has been developed, but the conventional technology has a problem in that it is not possible to observe the bacterial film on the tooth surface when the film has already formed or is expected to form in the early stages. In addition, in the case of a method for checking the bacterial film on the tooth surface using a chemically colored product, the aesthetics are reduced due to residual substances after use, and there is an inconvenience in that the thin film on the tooth surface to which the chemically colored product is adsorbed must be physically scraped off. Summary of the Invention [Problem to be solved by the invention]

[0006] The inventors of the present application have been conducting intensive research to develop a composition for staining tooth surfaces that allows observation of the areas where bacterial films are expected to form and the initial stages of bacterial films on teeth. As a result, they have discovered that riboflavin 5-phosphate sodium can stain not only biofilms but also acquired films, thereby completing the present invention.

[0007] Therefore, an object of the present invention is to provide a tooth surface coloring composition containing riboflavin 5-phosphate sodium.

[0008] A further object of the present invention is to provide a tooth surface coloring agent comprising a tooth surface coloring composition containing riboflavin 5-phosphate sodium. [Means for solving the problem]

[0009] The inventors of the present application have been conducting intensive research to develop a composition for staining tooth surfaces that allows observation of the areas where bacterial films are expected to form and the initial stages of bacterial films on teeth. As a result, they have discovered that riboflavin 5-phosphate sodium can stain not only biofilms but also acquired films.

[0010] The present invention relates to a tooth surface coloring composition containing riboflavin 5-phosphate sodium and a tooth surface coloring agent containing the same.

[0011] The present invention will now be described in more detail.

[0012] One aspect of the present invention relates to a tooth coloring composition comprising sodium riboflavin 5-phosphate.

[0013] In the present invention, "riboflavin 5-phosphate sodium" refers to a compound represented by the following chemical formula 1 and having the molecular formula C 17 H 24 N4NaO 11P refers to the sodium phosphate form of riboflavin, which has a molecular weight of 514.4 and is the major growth-promoting factor of the naturally occurring vitamin B complex.

[0014] Specific examples of the salt of riboflavin 5-phosphate sodium include, but are not limited to, riboflavin 5-phosphate sodium salt dihydrate and riboflavin 5-phosphate sodium salt hydrate.

[0015] [ka]

[0016] The composition may be capable of staining (dying) the bacterial film or acquired film on the tooth surface.

[0017] In the present invention, the term "tooth surface bacterial film" refers to the initial substance that forms tartar, also known as dental plaque, which is the main cause of tooth decay and periodontal disease, and refers to the state in which bacteria are attached to the acquired film and form colonies.

[0018] In the present invention, the term "acquired film" refers to an acellular, structureless organic film that forms on the surfaces of teeth, prostheses, dental plaque, artificial objects, etc., and is a thin, acquired film that is re-formed within a few minutes after brushing and plays an important role in protecting the teeth from acid while allowing bacteria to attach to the teeth.

[0019] The method for obtaining the riboflavin 5-phosphate sodium salt represented by the above formula 1 of the present invention is not particularly limited, and it can be chemically synthesized by a method known in the art, or a commercially available substance can be used.

[0020] The riboflavin 5-phosphate sodium may exist in a solvated form as well as in a nonsolvated form. The riboflavin 5-phosphate sodium of the present invention may exist in a crystalline or amorphous form, and all of these physical forms are within the scope of the present invention.

[0021] The riboflavin 5-phosphate sodium generates negatively charged riboflavin phosphate in aqueous solution, which can electrostatically bind to tooth surface bacterial and acquired pellicle films.

[0022] In this case, riboflavin phosphate emits light green to red fluorescence depending on the concentration when irradiated with 405 nm light, so after treatment with the composition of the present invention, the areas where bacterial films are expected to form on the tooth surface and the initial bacterial films on the tooth surface can be observed when irradiated with 405 nm light.

[0023] The concentration of the riboflavin 5-phosphate sodium may be 0.1-50.0mg / ml, 0.1-40.0mg / ml, 0.1-30.0mg / ml, 0.1-20.0mg / ml, 0.1-10.0mg / ml, 0.1-5.0mg / ml, 0.1-4.0mg / ml, 0.1-3.0mg / ml, 0.1-2.0mg / ml, or 0.1-1.0mg / ml. If the concentration of the riboflavin 5-phosphate sodium is less than 0.1mg / ml, the intensity of the fluorescence may be so low that the bacterial film on the tooth surface may not be observed. If the concentration of the riboflavin 5-phosphate sodium is more than 50.0mg / ml, the fluorescence intensity may be reduced due to the quenching effect of the fluorescent material, and the aesthetics may be damaged due to the residual material.

[0024] Meanwhile, the riboflavin 5-phosphate sodium of the present invention is a food additive and a water-soluble vitamin (without dosage limit) certified by the Ministry of Food and Drug Safety of Korea, and therefore has the advantage of being safe to use as a tooth surface coloring composition, which is an oral composition.

[0025] In addition, as described above, the riboflavin 5-phosphate sodium of the present invention emits fluorescence only when irradiated with 405 nm light and does not require separate washing. Therefore, it has advantages of being easy to use and aesthetically superior compared to conventional coloring compositions that require a fluorescent chemical coloring product to be placed on the tooth surface to check the color and a separate washing process to be followed after checking.

[0026] The formulation of the tooth surface coloring composition of the present invention is not particularly limited, and may be in the form of a powder, granules, tablets, emulsion, aerosol, soft or hard capsule, sterile injection solution or sterile powder, and may further contain a dispersant or stabilizer.

[0027] The tooth surface coloring composition of the present invention may contain commonly used abrasives, wetting agents, foaming agents, binders, sweeteners, pH regulators, preservatives, medicinal ingredients, fragrances, whitening agents, pigments, solvents, etc., depending on the formulation and purpose of use.

[0028] Another aspect of the present invention relates to a tooth surface coloring agent comprising a tooth surface coloring composition containing sodium riboflavin 5-phosphate.

[0029] In the present invention, the term "tooth surface coloring agent" refers to a preparation used for staining or coloring the bacterial film (dental plaque) or acquired film on the tooth surface.

[0030] The dosage form of the tooth surface coloring agent is not particularly limited, and may be a liquid, gel, cream, film, patch, powder, tablet, or solid preparation.

[0031] The common features between the tooth surface coloring composition of the present invention and the tooth surface coloring agent described above will be omitted here in order to avoid overly complicating the specification of the present application. Effect of the Invention

[0032] The present invention relates to a tooth surface coloring composition and a tooth surface coloring agent containing the same. The tooth surface coloring composition of the present invention is capable of not only coloring (staining) tooth surface bacterial membranes (biofilms), but also coloring (staining) the intended formation site of tooth surface bacterial membranes, i.e., acquired coatings, and is characterized in that it is possible to obtain a variety of information regarding the amount and properties of tooth surface bacterial membranes by analyzing the color and intensity of the fluorescence emitted by the riboflavin 5-phosphate sodium of the present invention. In particular, it is expected to be useful for observing early tooth surface bacterial membranes. [Brief description of the drawings]

[0033] [Figure 1a] FIG. 1a shows the results of evaluating the fluorescence intensity of a composition according to an embodiment of the present invention (left: white light, right: blue light) taken with a Qraycam Pro (AIOBIO, Seoul, Korea), and FIG. 1b shows a graph of the results measured with a fluorescence spectrometer. [Figure 1b] FIG. 1a shows the results of evaluating the fluorescence intensity of a composition according to an embodiment of the present invention (left: white light, right: blue light) taken with a Qraycam Pro (AIOBIO, Seoul, Korea), and FIG. 1b shows a graph of the results measured with a fluorescence spectrometer. [Diagram 2] 1 is a diagram showing the results of dyeing evaluation of an acquired coating of a composition according to an embodiment of the present invention (left: white light, right: blue light). [Diagram 3] 1 is a diagram showing the results of staining evaluation of a composition according to an embodiment of the present invention against Streptococcus mutans biofilm (left semicircle: control group, right semicircle: experimental group). [Figure 4] 1 is a diagram showing the results of staining evaluation of a composition according to an embodiment of the present invention against a polymicrobial biofilm (left semicircle: control group, right semicircle: experimental group). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0034] The present invention will be described in more detail with reference to the following examples. It will be obvious to those skilled in the art that these examples are provided solely for the purpose of illustrating the present invention in more detail, and that the scope of the present invention is not limited by these examples in accordance with the gist of the present invention.

[0035] Experimental Example 1. Evaluation of the fluorescence intensity of riboflavin 5-phosphate sodium (hereinafter referred to as RPS)

[0036] 100 mg / ml RPS stock solutions were prepared for each of sterile distilled water (DW, (1)), gargle (GG, Soo Green gargle, (2)), saliva (S(FX), (3)) and filtered saliva (S(FO), (4)), and then diluted to concentrations of 100, 50, 25, 12.5, 6.25, 3.12, 1.5, 0.78, 0.39, 0.19 and 0.1 mg / ml to prepare plates.

[0037] Each plate was photographed with Qraycam Pro (AIOBIO, Seoul, Korea) to obtain white and blue light images, and then the fluorescence intensity was measured using a fluorescence spectrometer (Varioskan, Excitation = 405 nm / Emission = 520 nm).

[0038] As shown in Figure 1, visual evaluation of the images showed that neither the white light (left in Figure 1a) nor the blue light (right in Figure 1a) images showed any difference in fluorescence between the solvents, and red fluorescence changed to green fluorescence as the concentration went from high (100 mg / ml) to low (0.01 mg / ml).

[0039] In addition, the fluorescence intensity of RPS was measured at various concentrations using a fluorescence spectrometer, and it was found that the fluorescence intensity increased and then decreased as the concentration increased from 0.01 mg / ml to 0.39 mg / ml. This increase and decrease did not differ depending on the solvent, and it was confirmed that the maximum fluorescence intensity was at a concentration of 0.4 mg / ml in all solvents (Figure 1b).

[0040] Experimental Example 2. Evaluation of staining for the acquired capsule (AP) of RPS

[0041] In order to evaluate whether RPS also stains the acquired film, which is a salivary component, the following experiment was performed.

[0042] Bovine tooth specimens were immersed in artificial saliva for 4 hours to form an artificial acquired film. The specimens on which the acquired film had been formed were then immersed in 2T (2-Tone), RPS50 (RPS 50mg / ml) and RPS0.4 (RPS 0.4mg / ml). After immersion, the specimens were washed three times in distilled water. Then, immediately after application of the stain (Application), after the first wash (1 st After the second washing (2 nd washing), and after the third washing (3 rd The degree of staining at each stage was confirmed by taking a video of the washing process (using Qraycam Pro).

[0043] [A dental plaque staining agent (2-Tone (2T)) currently in clinical use was diluted to a concentration of 10% and used as a control group, and two concentrations were used as experimental groups based on the results of Experimental Example 1 above: 50 mg / ml, which is the highest concentration at which RPS is completely dissolved, and 0.4 mg / ml, which has the strongest fluorescent intensity.]

[0044] As shown in Figure 2, immediately after application of the stain, both RPS50 and RPS0.4 stained the acquired capsule. After the third rinse, fluorescence was observed only from blue light (right side of Figure 2) for RPS50, while the fluorescence of RPS0.4 disappeared after rinsing. In particular, RPS50 showed a characteristic in which the fluorescence changed from red before rinsing to yellow after rinsing.

[0045] These results indicate that different fluorescence is observed depending on the amount of RPS remaining attached to the bacterial membrane on the tooth surface, suggesting that by analyzing the color and intensity of the fluorescence emitted by RPS, it may be possible to obtain more diverse information regarding the amount and properties of the bacterial membrane on the tooth surface.

[0046] Experimental Example 3. Evaluation of staining of RPS against Streptococcus mutans biofilms

[0047] Since S. mutans is a major pathogen in the oral cavity and frequently forms biofilms, we conducted the following experiment to evaluate the degree of RPS staining for biofilms using a single-species S. mutans biofilm model.

[0048] After forming an acquisition film on the bovine tooth specimen, S. mutans seeds were inoculated. As in Experimental Example 2 above, the specimens were divided into three groups (2T, RPS50, and RPS0.4), and matured biofilms were formed for 24 hours, 48 ​​hours, and 72 hours in each group. After that, Qraycam Pro images were taken immediately after applying the stain to the biofilm at each time point (24 hours, 48 ​​hours, and 72 hours) (no washing) and after the third washing with water (after washing 3 times). At this time, the images of the experimental results of the acquisition film in Experimental Example 2 above were used as control images.

[0049] As shown in Figure 3, immediately after applying the stain, RPS50 showed red fluorescence that spread over the entire specimen, and after the third water wash, the fluorescence changed from yellow to yellow + red as the incubation time increased.

[0050] Immediately after application of the stain, for RPS0.4, only faint yellow fluorescence was observed from the 24-hour biofilm, while red fluorescence was observed in the center of the specimen from the 48-hour and 72-hour biofilms. After the third wash, almost no fluorescence was observed from the 24-hour biofilm, faint yellow fluorescence from the 48-hour biofilm, and slight red fluorescence from the 72-hour biofilm.

[0051] These results indicate that different colors of fluorescence are observed depending on the amount of RPS remaining attached to the bacterial membrane on the tooth surface and the maturity of the bacterial membrane on the tooth surface. This suggests that by analyzing the color and intensity of the fluorescence emitted by RPS, it may be possible to obtain more diverse information regarding the maturity, quantity, and properties of the bacterial membrane on the tooth surface.

[0052] Experimental Example 4. Evaluation of RPS staining for microcosm biofilms

[0053] Oral dental plaque is a community of polymicrobial microorganisms, so we used a polymicrobial microcosm biofilm model that mimics this and conducted the following experiment to evaluate the degree of RPS staining in the biofilm.

[0054] Bovine tooth specimens were inoculated with irritating saliva to form a polymicrobial biofilm. As in Experimental Example 2 above, the specimens were divided into three groups (2T, RPS50, and RPS0.4), and the stain was applied to the biofilm formed for 24 hours, 48 ​​hours, and 72 hours per group. Then, Qraycam Pro images were taken immediately after the stain was applied to the biofilm at each time point (24 hours, 48 ​​hours, and 72 hours) (no washing) and after the third washing (after washing 3 times). In this case, the image of the experimental result of the acquired coating in Experimental Example 2 above was used as a control image.

[0055] As shown in Figure 4, no significant differences were observed compared to the results of the S. mutans biofilm in Experimental Example 3. However, the overall amount of biofilm was observed to be small, which can be interpreted as the result of the inhibition of the formation of a bacterial film on the tooth surface due to the interaction and competition between the various bacteria in the biofilm of a polymicrobial community.

[0056] The tooth surface coloring composition of the present invention can not only color (stain) the tooth surface bacterial film (biofilm), but also the planned formation site of the tooth surface bacterial film, i.e., the acquired film, and is characterized in that it can obtain a variety of information about the amount and properties of the tooth surface bacterial film by analyzing the color and intensity of the fluorescence emitted by the riboflavin 5-phosphate sodium of the present invention, and is expected to be particularly useful for observing the initial stage of the tooth surface bacterial film.

Claims

1. A composition for coloring teeth, comprising: Contains sodium riboflavin 5-phosphate, The composition provides color to the acquired coating. A composition for coloring teeth.

2. The composition stains the bacterial film on the tooth surface. The composition of claim 1.

3. The riboflavin 5-phosphate sodium was included at a concentration of 0.1 to 50.0 mg / ml. The composition of claim 1.

4. The composition is in the form of a powder, emulsion, aerosol, or soft or hard capsule. The composition of claim 1.

5. The composition emits fluorescence when irradiated with 405 nm light. The composition of claim 1.

6. The composition does not require separate washing after staining the teeth. The composition of claim 1.

7. The composition according to any one of claims 1 to 6 is included. A tooth surface coloring agent characterized by the above.

8. The tooth coloring agent is in the form of a liquid, gel, cream, powder, film, patch, tablet, or solid. The tooth surface coloring agent according to claim 7.

9. The tooth coloring agent does not require separate washing after tooth coloring. The tooth surface coloring agent according to claim 7.

Citation Information

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