Dental disclosing composition and method for screening dental disclosing composition

Abstract

The present invention relates to a dental disclosing composition and a screening method therefor, and more specifically, to a dental disclosing composition comprising cacao pigment or gardenia blue pigment, and a screening method therefor. Containing a natural material that has stable chemical properties, food-grade usability, and dyeability, the composition is ingestible and suitable as a substitute for conventional disclosing solutions. Moreover, the composition is expected to be widely applicable as a means for evaluating the effectiveness of dental disclosing materials.

Description

Composition for coloring teeth and method for screening the composition for coloring teeth

[0001] The present invention relates to a composition for coloring teeth containing cocoa pigment or gardenia blue pigment and a screening method therefor.

[0002] Dental plaque is a film of bacteria that clings to the thin, sticky glycoprotein residue of microscopic food particles that remain on the teeth after eating. It is also called dental plaque, plaque, or biofilm. The bacteria in dental plaque produce acids that can cause tooth decay, such as dental caries, and release toxins that irritate the gums. Over time, they turn into tartar, which can cause periodontal disease, or gum disease.

[0003] Immediately after eating or when brushing your teeth incorrectly, plaque, a clump of bacteria, initially attaches to teeth in small areas. If left untreated, it gradually accumulates and spreads across the entire surface of the teeth, leaving a dry mouth and causing bad breath. If plaque remains in the oral cavity for a long time and is not easily removed, it absorbs calcium from saliva and gradually hardens into tartar. Tartar attaches not only to the surface of the teeth but also to the roots of the teeth, causing inflammation of the gums. As plaque accumulates and builds up towards the roots of the teeth, it separates the teeth from the gums and reduces the amount of root bone embedded in the jaw, ultimately leading to tooth loosening or loss. Plaque is difficult to see with the naked eye, but when a stain is applied to the teeth, the pigment of the stain penetrates the crevices of the plaque, staining the entire plaque, making it clearly visible to the naked eye.

[0004] Tooth discoloring solutions are preparations used to stain dental plaque in the oral cavity for oral hygiene purposes. Tooth discoloring solutions have been commercially available in liquid, tablet, lozenge, and gel forms. However, in 2015, they were reclassified from medical devices to over-the-counter drugs in compliance with standards in the US and Europe. Since then, both domestic and international products have been required to undergo safety and efficacy testing, leading to a halt in sales and distribution. Recently, reports of cytotoxicity to gingival fibrous tissue have surfaced, and the FDA has also suspended the use of tar dyes such as Red No. 2 in food. The FDA is considering discontinuing the use of water-soluble tar dyes (erythrosine) in pharmaceuticals due to adverse effects such as the development of thyroid tumors in animal testing. However, approval for their use continues due to the lack of alternatives. Accordingly, there is a need to develop alternative candidates for tooth surface staining through the discovery of substances that can replace existing tooth surface staining agents and clinical evaluation of their effectiveness to objectively evaluate their effectiveness.

[0005] One aspect is to provide a composition for coloring teeth containing cocoa pigment or gardenia blue pigment.

[0006] Another aspect is to provide a tooth colorant comprising the composition.

[0007] Another aspect provides a method of coloring a tooth surface comprising the step of applying the composition to the tooth surface of an individual in need thereof.

[0008] Another aspect is that the composition provides a use for use in the manufacture of a colorant.

[0009] Another aspect provides a method for screening a dental staining agent, including the steps of: a) measuring the dental plaque staining area of ​​a candidate substance; b) measuring the staining area of ​​an existing dental staining agent to be used as a positive control; c) calculating a staining rate by dividing the area measured in a) by the sum of the area values ​​measured in a) and the area values ​​measured in b); and d) selecting a substance having a staining rate calculated in step c) of 90% or more as a dental staining agent.

[0010] Each description and embodiment disclosed in this invention can also be applied to each other description and embodiment. That is, all combinations of the various elements disclosed in this invention fall within the scope of this invention. Furthermore, the scope of this invention is not limited by the specific descriptions described below.

[0011] The configuration of the present invention is described in detail below.

[0012] One aspect provides a composition for coloring teeth containing cocoa pigment or gardenia pigment.

[0013] In one specific example, the composition can color dental plaque or acquired pellicle.

[0014] As used herein, the term "dental plaque" may refer to a film of bacterial clumps formed by oral bacteria adhering to a thin, sticky, glycoprotein residue of microscopic food particles that remain on the tooth surface after eating. The degree of staining of a dental staining agent can be compared based on the degree of staining of the dental plaque.

[0015] In this specification, the term “acquired pellicle” refers to a pellicle contained in saliva.

[0016] It can refer to a colorless, transparent, thin film-like attachment derived from glycoprotein that is attached to the tooth surface.

[0017] In one specific example, the cocoa pigment or gardenia pigment may be included in a weight ratio of about 0.1 to 10%, for example, 0.1 to 9%, 0.1 to 8%, 0.1 to 7%, 0.1 to 6%, 0.1 to 5%, 0.5 to 10%, 0.5 to 9%, 0.5 to 8%, 0.5 to 7%, 0.5 to 6%, 0.5 to 5%, 1 to 10%, 1 to 9%, 1 to 8%, 1 to 7%, 1 to 6%, 1 to 5%.

[0018] If the above-mentioned cocoa pigment or gardenia pigment is included in a weight ratio of less than 0.1% of the total composition, the coloring effect may be minimal, and if it is included in a weight ratio of 10% or more, the coloring effect may be strong, but problems may occur during the processing process because it is strongly dyed on the tooth surface after coloring.

[0019] In one specific example, the cacao color may refer to a pigment obtained by fermenting and roasting cacao beans, which are seeds of cacao (Theobroma cacao Linne), and then extracting them with a solvent. In addition, the gardenia blue pigment may refer to a pigment obtained by adding beta-glucosidase to a mixture of iridoid glycosides and protein hydrolyzates contained in a fruit extract of gardenia (Gardenia augusta Merrill or Gardenia jasminoides Ellis).

[0020] In one specific embodiment, the composition can exhibit a dyeing rate of greater than 90%, for example, a dyeing rate of 90 to 100%, 91 to 100%, 92 to 100%, 93 to 100%, 94 to 100%, 95 to 100%, 96 to 100%, 97 to 100%, 98 to 100%, or 99 to 100%.

[0021] In this specification, the term "dyeing rate" refers to a comparative evaluation of the dyeing rate that compares the degree of staining of dental plaque, which is a result of comparing the dyeing speed of dyes. The dyeing rate may refer to a value obtained by dividing the staining area of ​​a tooth coloring composition containing cocoa pigment or gardenia blue pigment by the sum of the staining area of ​​a tooth coloring composition containing cocoa pigment or gardenia blue pigment and the staining area of ​​a conventionally used tooth coloring agent.

[0022] The higher the above dyeing rate, the better the effect of the tooth surface dye can be judged.

[0023] In one specific example, the composition may be in any one formulation selected from the group consisting of, but not limited to, powder, cream, stick, balm, gel, mousse, emulsion, aerosol, spray, soft capsule and hard capsule.

[0024] As used herein, the term "stick" refers to a solid formulation, such as a stick or balm, and may be distinguished from a liquid or gel formulation. The shape of the stick may be, but is not limited to, a cylinder or a polygonal column. The stick formulation has an appropriate hardness and therefore exhibits excellent spreadability.

[0025] The composition may further comprise any conventional ingredients commonly used in over-the-counter drugs containing a tooth staining agent, for example, a base ingredient such as a solvent, a surfactant, a humectant, a pH adjuster, an oral care agent ingredient such as ethanol, purified water, glycerin, sodium fluoride, a thickener, a dispersant, a flavoring agent, a filler, a preservative, an antiseptic, a neutralizer, a sweetener, a vitamin, a free radical scavenger, a metal ion sequestering agent, a functional ingredient, and mixtures thereof. A person skilled in the art can select any of the additional ingredients and / or the amounts thereof such that the advantageous properties of the composition according to the present disclosure are not or are substantially not adversely affected by the expected addition.

[0026] Another aspect provides a tooth colorant comprising the composition.

[0027] Another aspect provides a method of coloring a tooth surface comprising the step of applying the composition to the tooth surface of an individual in need thereof.

[0028] Another aspect is that the composition provides a use for use in the manufacture of a colorant.

[0029] Another aspect provides a method for screening a dental staining agent, including the steps of: a) measuring the dental plaque staining area of ​​a candidate substance; b) measuring the staining area of ​​an existing dental staining agent to be used as a positive control; c) calculating a staining rate by dividing the area measured in a) by the sum of the area values ​​measured in a) and the area values ​​measured in b); and d) selecting a substance having a staining rate calculated in step c) of 90% or more as a dental staining agent.

[0030] In this specification, the term "candidate material" is not limited to any material for which a dyeing rate is to be compared in order to use the sample for coloring teeth, and may include both natural and synthetic materials. The natural material may be a natural pigment, for example, yellow pigment, red pigment, dark brown pigment, green pigment, or blue pigment, and specifically, may be, but is not limited to, safflower yellow, gardenia yellow, oleo-zin paprika, mongolic acid pigment, squid ink, cacao pigment, caramel pigment, green mixed pigment, blue mixed pigment, or gardenia blue pigment.

[0031] In this specification, the term “existing tooth surface staining agent” refers to a commercially available tooth surface staining agent that can serve as a positive control group to compare the tooth surface staining use of a candidate substance, and the type thereof is not particularly limited.

[0032] The method for measuring the colored area in steps a) and b) above may be to utilize the Image J program.

[0033] In the above step d), the dyeing rate may be 90% or more, for example, 90 to 100%, 91 to 100%, 92 to 100%, 93 to 100%, 94 to 100%, 95 to 100%, 96 to 100%, 97 to 100%, 98 to 100%, or 99 to 100%.

[0034]

[0035] Duplicate contents are omitted in consideration of the complexity of this specification, and terms not otherwise defined in this specification have meanings commonly used in the technical field to which the present invention belongs.

[0036] The present invention relates to a composition for coloring teeth containing cocoa pigment or gardenia blue pigment, wherein the composition is chemically stable and contains a natural substance with dyeing properties suitable for use as an edible substance, and is therefore ingestible and is expected to be utilized as a substitute for existing tooth coloring agents.

[0037] Figures 1a and 1b show the results of taking frontal photographs of the teeth of the experimental subject before tooth discoloration.

[0038] Figures 2a and 2b show the results of taking frontal photographs of teeth after applying a commercially available tooth coloring agent (control group) to experimental subjects.

[0039] Figure 3 shows the results of taking a frontal photograph of teeth after applying a tooth coloring agent containing cocoa pigment to the experimental subject.

[0040] Figure 4 shows the results of taking a frontal photograph of teeth after applying a tooth coloring agent containing turmeric pigment to the experimental subjects.

[0041] The following examples are provided for more detailed description. However, these examples are provided solely to illustrate one or more specific examples, and the scope of the present invention is not limited to these examples.

[0042]

[0043] Experimental Example 1. Sample and Experimental Preparation

[0044] For about 40 natural substances that can be used for food and have dyeing properties, the coloring rate and stability maintenance were evaluated using the existing commercialized foreign tooth colorants (Trace disclosing solution, USA) as the gold standard, and 10 substances (safflower yellow, gardenia yellow, oleo-zin paprika, red pigment, squid ink, cocoa color, caramel color, green color mixed color, blue color mixed color, gardenia blue) with stable chemical composition were derived from the tooth colorant base excluding the existing pigments. Each of the 10 natural substances derived as described above was included as a pigment component, and in addition, base components that can be commonly used in tooth surface coloring agents, such as solvent, surfactant, humectant, pH adjuster, and oral care agent components ethanol, purified water, glycerin, and sodium fluoride, were mixed in an appropriate weight ratio to manufacture a tooth surface coloring agent based on natural substances.

[0045]

[0046] Experimental Example 2. Comparative Evaluation of Dyeing Rates of Tooth Colorants

[0047] The area of ​​the stained area on the tooth surface was calculated using the Image J program from a total of eight images of central and lateral incisors that could be evaluated, and the stained area after applying the 10 types of natural substance-based tooth surface staining agents derived from Experimental Example 1 was compared with the staining rate of the stained tooth surface after applying the existing tooth surface staining agent (Trace disclosing solution, USA) to evaluate the results.

[0048] The dyeing rate comparison was measured based on the following [Formula 1].

[0049] [Formula 1]

[0050] Dyeing rate comparison = A / (A+B)

[0051] In the above [Formula 1], A represents the new natural material dental plaque staining area, B represents the dental plaque staining area of ​​the existing dental plaque staining agent (Trace disclosing solution, USA), and in the above [Formula 1], A+B represents applying the existing dental plaque staining agent (B) and then applying the natural material-based dental plaque staining agent (A) to clearly confirm the presence or absence of staining.

[0052] The results of confirming the dyeing rate using the method of [Formula 1] for 10 natural substances derived from Experimental Example 1 are as shown in [Table 1] below.

[0053] Comparative evaluation of natural material coloring rate Dyeing rate (N=8) Standard deviation Yellow Safflower yellow 28.5% 10.1 Gardenia yellow 0.0% 0.0 Red Oleozin Paprika 10.8% 6.7 Red yeast red 30.0% 16.3 Dark brown Squid ink 53.3% 8.0 Cocoa pigment 98.7% 0.9 Caramel pigment 5.8% 3.1 Green Green mixed color 11.7% 6.2 Blue Blue mixed color 7.8% 5.9 Gardenia blue 99.9% 0.2

[0054] From the above results, it was confirmed that cocoa pigment and gardenia pigment showed excellent effects as colorants with a dyeing rate of over 90%.

[0055] For a more visible comparison of staining rates, the teeth surfaces of the subjects of the tooth staining experiment were photographed before tooth staining and are shown in Figs. 1a and 1b. After applying the prepared tooth staining agent to the subjects of the tooth staining experiment, a frontal photograph was taken, and then the existing tooth staining agent was applied and the additionally stained teeth surfaces were photographed. The frontal photographs of the teeth to which the existing tooth staining agent was applied are shown in Figs. 2a and 2b, and the frontal photographs of the teeth to which the tooth staining agent prepared by Experimental Example 1, including cocoa pigment or gardenia blue pigment, was applied are shown in Figs. 3 and 4.

[0056]

[0057] Experimental Example 3. Oral Tooth Colorant Toxicity Test (in vivo)

[0058] In order to conduct a single oral administration toxicity test on the tooth staining agent derived from Experimental Example 1, among the 10 natural tooth staining substances derived from Experimental Example 1, a tooth staining agent containing gardenia blue pigment was administered to SD rats at a high dose of up to 2000 mg / kg BW in accordance with the "Standards for Toxicity Tests for Pharmaceuticals, etc." of the Ministry of Food and Drug Safety Notice. The dose ratio was set to 2, and the intermediate and low doses were set to 1000 and 500 mg / kg BW, respectively. The female and male models were fasted for approximately 18 hours, and the test substance was administered orally once into the stomach using a syringe equipped with an oral administration sonde. Mortality, general symptoms, and body weight changes were observed for 14 days after administration, and the surviving animals were necropsied and examined macroscopically for abnormalities in the organs. Sterile distilled water was administered as a control group. The administration conditions are as follows [Table 2].

[0059] Distinction by sex Number of animals Administered dose (mg / kg BW) Amount of administered solution (mL / kg BW) Route of administration Control group Male 5010 Oral Female 5 Example 1 Male 5500 Female 5 Example 2 Male 51000 Female 5 Example 3 Male 52000 Female 5

[0060] All experimental groups were observed at least once a day for 14 days after administration. However, on the day of administration, observations were made at 0.5, 1, 2, 3, and 4 hours after administration, and no deaths or abnormal findings were observed due to administration.

[0061] Meanwhile, as shown in [Table 3] below, weight gain was observed in all treatment groups. Therefore, the weight data were statistically analyzed using the SPSS (Ver. 19.0) statistical program. First, a homogeneity test was performed using Levene's test, followed by a one-way ANOVA test. No significant differences were observed in the one-way ANOVA test. The confidence interval was set at 95%.

[0062] That is, no statistically significant difference was confirmed between the example and control groups.

[0063] Distinctive Dose (mg / kg BW) Sex - Time after administration 0714 Control group 0 Male body weight average 136.72 17.72 71.6 Standard deviation 3.8 2.8 7.2 Number of animals 555 Female body weight average 103.5 155.4 173.2 Standard deviation 5.0 9.3 12.9 Number of animals 555 Example 1500 Male body weight average 133.42 14.3 260.4 Standard deviation 3.9 5.8 10.6 Number of animals 555 Female body weight average 101.2 157.3 175.8 Standard deviation 3.5 6.0 9.2 Number of animals 555 Example 2 1000 Male weight average 134.6 208.8 268.1 Standard deviation 5.6 7.2 5.8 Number of animals 555 Female weight average 99.1 158.5 175.2 Standard deviation 5.4 8.5 7.3 Number of animals 555 Example 3 2000 Male weight average 136.4 220.8 271.0 Standard deviation 5.4 8.3 10.9 Number of animals 555 Female weight average 102.0 157.1 175.1 Standard deviation 4.0 6.2 7.0 Number of animals 555

[0064] In addition, 14 days after administration of the dental staining agent, all surviving animals were examined for appearance, then sacrificed by exsanguination under isoflurane anesthesia and their organs were visually examined. As a result, it was confirmed that no abnormal organs were found.

[0065]

[0066] In conclusion, no toxicological findings related to the administration of Examples 1 to 3 were found when a single oral administration of a dental staining agent to rats was performed, and thus the lethal dose based on the toxicity test results was confirmed to be 2000 mg / kg BW or more for both males and females.

Claims

1. A composition for coloring teeth containing cocoa pigment or gardenia pigment.

2. In claim 1, the composition is a composition that colors dental plaque or acquired pellicle.

3. In claim 1, the composition exhibits a tooth surface color absorption rate of 90% or more.

4. A composition according to claim 1, wherein the composition comprises cocoa pigment or gardenia pigment in an amount of about 0.1 to 10% by weight.

5. A tooth colorant comprising the composition of claims 1 to 4.

6. A method for coloring a tooth surface, comprising the step of applying an effective amount of the composition of claim 1 to the tooth surface of an individual in need thereof.

7. Use of the composition of claim 1 for the manufacture of a tooth colorant. 8.a) Step of measuring the dental plaque staining area of ​​the candidate substance; b) A step of measuring the stained area of ​​an existing tooth staining material to be used as a positive control; c) a step of calculating the dyeing rate by dividing the area measured in a) by the sum of the area value measured in a) and the area value measured in b); and d) A method for screening a tooth colorant, comprising a step of selecting a material having a dyeing rate of 90% or more calculated in step c) as a tooth colorant.

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