PREPARATION FOR ORAL CAVITY

Abstract

The present invention provides a preparation for attaching to teeth or tooth peripheries. The preparation for attaching to teeth or tooth peripheries of the present invention can give high adhesive force to the desired site despite interproximal space or curves of teeth. It is easy to hand while controlling drug release.

Claims

1. A preparation for attaching to teeth or tooth peripheries, wherein the preparation comprises a slime hydrogel containing a synthetic silica or an alginate compound.

2. The preparation for attaching to teeth or tooth peripheries of claim 1, wherein the synthetic silica is at least one selected from silica powder, fumed silica, precipitated silica, colloidal silica, aerogel and silica sol.

3. The preparation for attaching to teeth or tooth peripheries of claim 1, wherein the alginate compound is calcium alginate, potassium alginate, sodium alginate, triethanolamine alginate or a mixture thereof.

4. The preparation for attaching to teeth or tooth peripheries of claim 1, wherein the alginate compound is contained in an amount of 0.1 wt % to 20 wt % based on the total weight of the preparation.

5. The preparation for attaching to teeth or tooth peripheries of claim 1, wherein the hydrogel comprises polyvinyl alcohol (PVA) and a salt forming cross-links with —OH groups of the polyvinyl alcohol.

6. The preparation for attaching to teeth or tooth peripheries of claim 5, wherein the salt forming cross-links with —OH groups of the polyvinyl alcohol is borate, phosphate or a mixture thereof.

7. The preparation for attaching to teeth or tooth peripheries of claim 1, which comprises a medicinal ingredient for intra-oral delivery.

8. The preparation for attaching to teeth or tooth peripheries of claim 7, wherein the medicinal ingredient is sodium fluoride, stannous fluoride, indium fluoride, amine fluoride, sodium monofluorophosphate, tetrasodium pyrophosphate (TSPP), sodium acid pyrophosphate (SAPP), sodium tripolyphosphate (STP), sodium potassium pyrophosphate, tetrapotassium pyrophosphate, acidic sodium metaphosphate, acidic sodium polyphosphate, triclosan, chlorhexidine, alexidine, hexetidine, sanguinarine, benzalkonium chloride, salicylanilide, domiphen bromide, cetylpyridinium chloride (CPC), tetradecylpyridinium chloride (TPC), aspirin, ketorolac, flurbiprofen, piroxicam, meclofenamic acid, thiamine, riboflavin, nicotinic acid, pantothenic acid, pyridoxine, biotin, folic acid, vitamin B 12, lipoic acid, ascorbic acid, vitamin A, vitamin D, vitamin E, vitamin K, titrated extract of Zea Mays L. unsaponifiable fraction, Magnoliae Cortex extract, Myrrha, Rhatany, Chamomile, policresulen, titrated extract of Centella Asiatica, nutmeg extract, dexpanthenol, β-sitosterol, acetyl salicylic acid, zinc chloride, potassium phosphate, potassium diphosphate, calcium chloride, oxalic acid, potassium oxalate, ferric oxalate or a mixture thereof.

9. A preparation for attaching to teeth or tooth peripheries, which comprises a medicinal ingredient, a phase transition compound, a polymer that is water-insoluble but ethanol-soluble, and ethanol as a solvent, wherein the preparation is applied in liquid to teeth or tooth peripheries, and phase transited by saliva in the oral cavity, thereby having adhesiveness to teeth or tooth peripheries.

10. The preparation for attaching to teeth or tooth peripheries of claim 9, wherein the phase transition compound is selected from glyceryl monooleate, glyceryl monolinoleate, glyceryl monoarachidonate, glyceryl monostearate or a mixture thereof.

11. The preparation for attaching to teeth or tooth peripheries of claim 9, wherein the phase transition compound is contained in an amount of 5 wt % to 80 wt % based on the total weight of the preparation.

12. The preparation for attaching to teeth or tooth peripheries of claim 9, wherein the polymer that is water-insoluble but ethanol-soluble is ethyl cellulose, butyl ester of PVM/MA copolymer, polyvinyl acetate, polyvinyl acetate-phthalate, shellac, rosin, methacrylic acid copolymer or a mixture thereof.

13. A preparation for attaching to teeth or tooth peripheries of claim 9, which has viscosity of 10,000 cPs or less before being in contact with water, but has phase transited to gel or solid having adhesiveness to teeth or oral tissues after being applied to teeth or oral cavity.

14. The preparation for attaching to teeth or tooth peripheries of claim 13, which comprises the polymer that is water-insoluble but ethanol-soluble and the phase transition compound.

15. The preparation for attaching to teeth or tooth peripheries of claim 13, which comprises both of: a polymer selected from glyceryl monooleate, glyceryl monolinoleate, glyceryl monoarachidonate, glyceryl monostearate or a mixture thereof; and a polymer selected from ethyl cellulose, butyl ester of PVM/MA copolymer, polyvinyl acetate, polyvinyl acetate-phthalate, shellac, rosin, methacrylic acid copolymer or a mixture thereof.

16. The preparation for attaching to teeth or tooth peripheries of claim 9, wherein the medicinal ingredient is sodium fluoride, stannous fluoride, indium fluoride, amine fluoride, sodium monofluorophosphate, tetrasodium pyrophosphate (TSPP), sodium acid pyrophosphate (SAPP), sodium tripolyphosphate (STP), sodium potassium pyrophosphate, tetrapotassium pyrophosphate, acidic sodium metaphosphate, acidic sodium polyphosphate, triclosan, chlorhexidine, alexidine, hexetidine, sanguinarine, benzalkonium chloride, salicylanilide, domiphen bromide, cetylpyridinium chloride (CPC), tetradecylpyridinium chloride (TPC), aspirin, ketorolac, flurbiprofen, piroxicam, meclofenamic acid, thiamine, riboflavin, nicotinic acid, pantothenic acid, pyridoxine, biotin, folic acid, vitamin B12, lipoic acid, ascorbic acid, vitamin A, vitamin D, vitamin E, vitamin K, titrated extract of Zea Mays L. unsaponifiable fraction, Magnoliae Cortex extract, Myrrha, Rhatany, Chamomile, policresulen, titrated extract of Centella Asiatica, nutmeg extract, dexpanthenol, β-sitosterol, acetyl salicylic acid, zinc chloride, potassium phosphate, potassium diphosphate, calcium chloride, oxalic acid, potassium oxalate, ferric oxalate or a mixture thereof.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0111] FIG. 1 shows PVM/MA that is an example of a polymer which can control hardening rate of a phase transition compound according to the present invention (left), and illustrates structure of the formed alginate-calcium complex (right).

[0112] FIG. 2 shows hardness change checked after 1 min from mixing of the preparation. The unit of the vertical axis is denoted by g. As can be seen from FIG. 2, it can be found that in the case of Examples, harness is more rapidly increased from right after mixing the preparation to after 1 min from the mixing, and after 1 min from the mixing, hardness of Examples is higher than that of Comparative Examples. Namely, it can be confirmed that after 1 min from the mixing, the preparations of Examples are easier for users to handle than those of Comparative Examples.

[0113] FIG. 3 show hardness change checked from just before mixing to after 10 min from the mixing. As can be seen from FIG. 3, it can be found that after 10 min from mixing, hardness of the preparations of Examples is lower than that of Comparative Examples. Namely, it can be found that Comparative Examples harden harder after a certain period of time from the attachment.

[0114] FIG. 4 is a drawing prefiguratively showing the process that the preparation according to one embodiment of the present invention is hardening after applying and adhering the preparation to teeth. As can be seen from FIG. 4, the preparation of the present invention can reach up to interproximal space.

[0115] T refers to teeth, and 10 refers to a preparation for attaching to teeth or tooth peripheries.

DETAILED DESCRIPTION OF INVENTION

[0116] Hereinafter, the present invention will be described in more detail through the following embodiments. However, the embodiments according to the present invention may be modified in many different forms, and the scope of the present invention shall not be construed as being limited to the embodiments described below. The embodiments of the present invention are provided for illustration to help a full understanding of the present invention. Unless stated otherwise, % used herein is understood to mean wt %.

EXAMPLES

[0117] [Preparation of Mouth Band and Oral Preparation]

[0118] Examples and Comparative Examples were manufactured according to the following method.

[0119] The preparations were manufactured according to the following composition by adjusting to 50° C. and then mixing with a mechanical mixer.

TABLE-US-00001 TABLE 1 Example 1 Example 2 Example 3 PVA 2.8% PVA 2.8% PVA 2.8% Magnoliae 0.05% Centella 0.02% Zinc 0.1% Cortex extract chloride extract ethanol 1.0% TPP 10.0% ethanol 1.0% Borax 1.2% Aerosil200 1.2% Borax 1.2% Aerosil200 2.4% Water to 100% Sodium 0.3% Water to 100% Alginate Water to 100%

TABLE-US-00002 TABLE 2 Comparative Example 4 Comparative Comparative Comparative (P&G Example 1 Example 2 Example 3 SensiStop ™) PVA 2.8% PVA 10% PVA 2.8% Cellulose Magnoliae 0.05% Centella 0.02% Zinc 0.1% Gum. Cortex extract chloride Carbomer, extract ethanol 1.0% TPP 10.0% NaOH, ethanol 1.0% Water to 100% Water to 100% Glycerin, Borax 1.2% Water Water to 100%

[0120] [Evaluation of Adhesive Force in Interproximal Space and Buccal Surface]

[0121] 1. Test for Comparison of Interproximal Space and Buccal Surface Adhesive Force (Applying Method for Removing Artificial Dental Plaque)

[0122] (1) Test Method [0123] Evaluation device: ITPlus 4.0 Microcam [0124] Evaluation method: Before and after attachment of Comparative Examples and Examples, rate for removing artificial dental plaque on interproximal space and buccal surface was compared by area

[0125] a) Method for Coating Artificial Dental Plaque on Artificial Dental Model

[0126] Among gnathostaic models, maxillary posterior buccal surface that is easy to apply a troothbrush was inserted into a polymer (containing Red Dye) for 10 sec. After removing it, it was dried at room temperature for 60 min and then dried again in a drying room for 60 min to manufacture artificial dental plaque.

[0127] b) Test Method for Interproximal Space and Buccal Surface Adhesive Force

[0128] Examples and Comparative Examples were sprayed with a small amount of water to adjust the humid oral conditions and then adhered to the artificial dental plaque coated artificial teeth to be tested. Then, the artificial dental plaque on the interproximal space and the frontal surface of the tooth was removed by removing the preparation after 10 min under the same conditions, and then area of the interproximal space and the buccal surface was measured and compared.

[0129] (2) Test Result

[0130] The area of the artificial dental plaque removed from the interproximal space and the frontal surface by the use of Example and Comparative Example was measured. (The large area of plaque removal reflects the high adhesive force at that location)

TABLE-US-00003 TABLE 3 Comparative Comparative Area Example 1 Example 2 Example 1 Example 4 Interproximal 30.01 28.90 25.80 10.55 space Buccal surface 89.98 85.33 79.12 70.11

[0131] As can be seen from Table 3, Examples 1 and 2 showed large area of plaque removal at both of the interproximal space and the buccal surface. From the above result, it can be found that Examples 1 and 2 have excellent ability to be adhered up to the interproximal space, and it also can be found that those have low flowability and can secure sufficient contact time with the buccal surface, thereby having excellent ability to remove plaque from the buccal surface.

[0132] [Test for Comparison of Shape Retention Force and Length Extendibility]

[0133] 1. Shape Retention Force

[0134] After attaching Example and Comparative Example to the dental model consisting of both the upper jaw and the lower jaw, the time at which shape was not maintained and the preparation began to flow was recorded to evaluate whether there is physical strength to maintain the attached shape during use time. Using the dental model, the preparation was attached to the maxillary area to cover about three or more boundary areas between gums and teeth. After 10 min, whether the preparation flows down to the mandibular area or maintains the attachment state was observed. Then, using 5-point scale, if the shape is maintained same as initial stage, it is marked as 5 point, if the preparation slightly flows down but the shape and the position are maintained, it is marked as 4 point, if the shape and the position are slightly off while flowing down, it is marked as 3 point, if the shape and the position are much off, it is marked as 2 point, and if the shape and the position are completely off from the attachment site, it is marked as 1 point.

TABLE-US-00004 TABLE 4 Comp. Comp. Comp. Comp. Exam. Exam. Exam. Exam. Exam. Exam. Exam. 1 2 3 1 2 3 4 Shape 5 5 5 3 2 2 4 retention force

[0135] 2. Test for Comparison of Stretchable and Malleable Properties

[0136] For Examples showed excellent shape retention force in Table 4, length extendibility was further tested.

[0137] 1 g of Example was taken and placed on a PET sheet in the size of 1 cm*1 cm, another PET sheet was placed thereon, and then the length that could be maximally extended without tearing or puncturing the sheet by pressing with a finger was measured and compared.

TABLE-US-00005 TABLE 5 Example 1 Example 2 Example 3 Comparative Example 4 Extended 6 times 8 times 1.5 times Not extended when length pressed in product state

[0138] As can be seen from Table 5, it can be found that Examples attached to the tooth surfaces have excellent shape retention force and excellent length extendibility, and therefore those have stretchable characteristic. In particular, Comparative Example 4 didn't show significant difference from Examples of the present invention in terms of shape retention force, but it had a characteristic in which the length was not extended when pressed. Due to this difference, the preparation of Comparative Example 4 was difficult to be completely adhered up to the interproximal space. However, the preparation of the present invention was able to have perfect adhesive force in consideration of curves or gaps of teeth.

[0139] [Survey for Convenience of use to Human Subject (Adhesive Force, Shape Retention Force, Adhesive Force, Removability and the like)]

[0140] 1) Test subject and instructions: A total of 10 volunteers were asked to use Examples 1 to 3 and Comparative Examples 1 to 4 alternately three times, respectively, and then survey was conducted using 5-point Likert scale.

[0141] 2) Criteria

[0142] 5: Very satisfied

[0143] 4: Relatively satisfied

[0144] 3: Moderate

[0145] 2: Little unsatisfied

[0146] 1: A lot unsatisfied

[0147] As guideline, if the preparation was easily attached to the desired position and stuck to the place for the desired time where it was attached, the adhesive force was evaluated to be excellent, if the preparation was attached to the desired position and then it maintained the shape well without flowing down, the shape retention force was evaluated to be excellent, and if the preparation was easily adhered to the interproximal space or the boundary between teeth and gums by lightly pressing it with a finger, the adhesive force was evaluated to be excellent. Then, survey for removability was conducted according to the following 5-point Likert scale.

[0148] 5 : Removal is very convenient and there is no residue on teeth.

[0149] 4 : Removal is convenient but there is little residue.

[0150] 3 : Removal is inconvenient and there is inconvenience due to residue.

[0151] 2 : Removal is inconvenient and there are many residues.

[0152] 1 : Removal is very inconvenient and there are so many residues.

[0153] 3) Test result

TABLE-US-00006 TABLE 6 Comp. Comp. Comp. Comp. Exam. Exam. Exam. Example Example Example Example 1 2 3 1 2 3 4 Adhesive 4 4 4 4 4 2 2 force Shape 5 5 5 3 2 2 4 retention force Adhesive 5 5 5 5 2 5 3 force Removability 5 5 5 4 2 4 2

[0154] As can be seen from Table 6, Examples were able to obtain very excellent results overall in terms of adhesive force. Namely, the degree of flowing down after attachment was less than that of Comparative Examples.

[0155] Further, Examples obtained good result in terms of adhesive force, but when considering the shape retention or adhesive force overall, Examples obtained more excellent sense of use result.

[0156] [Survey for Clinical Sensitive Teeth or Gingivitis Relief to Human Subject]

[0157] 1) Test subject and instructions: Examples 1 to 3 and Comparative Examples 1 to 4 were attached to sensitive teeth or gum pain area for 10 min once a day and then removed.

[0158] 2) For each group, 15 volunteers who experienced sensitive teeth or gum pain were asked to use for 1 week and then survey was conducted according 5-point Likert scale.

[0159] 5: Sensitive teeth/gum pain relief effect lasted for one month in all attached sensitive teeth/gum pain areas.

[0160] 4: Sensitive teeth/gum pain relief effect was definitely felt in all attached sensitive teeth/gum pain areas.

[0161] 3: Sensitive teeth/gum pain relief effect was definitely felt in at least one attached sensitive teeth/gum pain area.

[0162] 2: Sensitive teeth against cold food or gum pain after eating became less sensitive, compared to before use.

[0163] 1: Sensitive teeth or gum pain relief effect was not felt.

[0164] The survey results of efficacy of Example and Comparative Example were obtained as follows.

TABLE-US-00007 TABLE 7 Comp. Comp. Comp. Comp. Exam. Exam. Exam. Example Example Example Example 1 2 3 1 2 3 4 Sensitive — — 4 — — 3 3 teeth relief Gingivitis 4 4 — 3 1 — — relief

[0165] As can be seen from Table 7, mouth bands of Examples showed more excellent efficacy in the oral cavity than those of Comparative Examples. Mouth bands of Examples had excellent adhesive force to the target site in the oral cavity and could deliver the drug up to the interproximal space. Therefore, those are advantageous to achieve the desired effect. Further, sufficient contact time could be secured and therefore drug delivery was easy.

[0166] [Preparation of Oral Preparation]

[0167] Oral preparations of Examples and Comparative Examples having the following composition were manufactured or purchased.

[0168] Examples and Comparative Examples were manufactured according to the following method.

[0169] The preparations were manufactured according to the following composition by adjusting the temperature of the second formulation to 50° C. and then mixing with a mechanical mixer. The amount of the alginate powder mixed with the second formulation was 100 times to the weight of the second formulation.

TABLE-US-00008 TABLE 8 Example 4 Example 5 Example 6 First Alginate powder Alginate powder Alginate powder formulation Second Zinc chloride 2.0% Magnoliae Cortex 0.1% Hydrogen peroxide 6.0% formulation (medicinal ingredient) extract (medicinal ingredient) PVM/MA 0.2% (medicinal ingredient) PVM/MA 1.0% Water to 100% PVM/MA 0.35% Water to 100% Water to 100% Comparative Comparative Comparative Example 5 Example 6 Example 7 First Alginate powder Alginate powder Alginate powder formulation Second Zinc chloride 2.0% Magnoliae Cortex 0.1% Hydrogen peroxide 6.0% formulation (medicinal ingredient) extract (medicinal ingredient) Water to 100% (medicinal ingredient) HPMC 1.0% PVA 0.35% Water to 100% Water to 100%

[0170] [Hardness Comparison Test (Test Method: Measured by using Texture Analyzer)]

[0171] Evaluation device: Stable Micro System TA XT Plus

[0172] Evaluation method: Hardness of Comparative Example and Example was measured by using Texture Analyzer

[0173] Hardness was measured at compression test mode of TA (Texture Analyzer). After filling 20 g of Example and Comparative Example into a 50 mL beaker, a 20 mm diameter aluminum probe for hardness measurement was set, and then hardness was measured with test speed of 1.5 mm/s, distance as target mode and distance of 10 mm. The hardness calculated from the device is the peak value of the first cycle.

[0174] Test result

[0175] The first formulations and the second formulations of Examples and Comparative Examples listed in Table 8 were mixed and then the results of comparison of hardness with time were shown in the following Table 9.

TABLE-US-00009 TABLE 9 Comp. Comp. Comp. Example Example Example Example Example Example 4 5 6 5 6 7 1 min from 150 g 180 g 340 g 109 g 120 g 80 g mixing 3 min 260 g 280 g 810 g 14,800 g 180 g 15,000 g 5 min 2,400 g 1600 g 2,100 g 21700 g 5,000 g 20,000 g 10 min 12,000 g 5,600 g 5,400 g 22600 g 16,000 g 22,400 g

[0176] As can be seen from Table 9, in the initial stage after mixing, the hardness values of Examples were higher and it was easy to apply to teeth or to be handled easily, and until 10 min after mixing, there was no large hardness change, so it was convenient to remove and easy to use without any irritation. The results of graphically representing the hardness change according to Examples and Comparative Examples were shown in FIG. 2 and FIG. 3.

[0177] [Test for Sense of use after Attachment]

[0178] Test for sense of use was carried out using the preparations having the composition according to Table 8. The first formulation and the second formulation were mixed just before use, and then the mixture was applied on a backing layer. The preparation was attached to the desired site using the backing layer and then pressed with a finger to be adhered. It is not necessary to remove the backing layer, but in the test, the backing layer was removed after 2 min from the attachment. After 10 min from the attachment, the preparation was removed.

[0179] 1. Survey for Adhesive Force

[0180] 30 Respondents were asked to use each of the preparations of Comparative Examples 5 to 7 and Examples 4 to 6 depending on the group according to the above instructions. Then, each group changed and used the products and then responded to a questionnaire for adhesive force to gaps between teeth (interproximal space).

[0181] Criteria for Survey Response

[0182] 5: Adhered well to gums and gaps between teeth by lightly pressing with a finger and easily removed

[0183] 4: Adhered to gaps between teeth by lightly pressing with a finger but adhesive force to gums is moderate.

[0184] 3: Adhered to gaps between teeth by lightly pressing with a finger but adhesive force to gums is weak.

[0185] 2: Adhesive force to teeth is strong, but adhesive force to gaps between teeth is weak.

[0186] 1: Adhesive force to teeth is strong, but adhesive force to gums is weak.

[0187] 2. Survey for Removability

[0188] 30 Respondents per group were asked to use each of the preparations of Comparative Examples 5 to 7 and Examples 4 to 6 according to the above instructions. Then, each group changed and used the products and then responded to a questionnaire for removability.

[0189] Criteria for Survey Response

[0190] 5: Removal is very convenient and there is no residue on teeth.

[0191] 4: Removal is convenient but there is little residue.

[0192] 3: Removal is inconvenient and there is inconvenience due to residue.

[0193] 2: Removal is inconvenient and there are many residues.

[0194] 1: Removal is very inconvenient and there are so many residues.

[0195] 3. Survey for Clinical Sensitive Teeth or Gum Pain Relief to Human Subject

[0196] 1) Test subject and instructions: Example 5 and Comparative Example 1 were attached to sensitive teeth or gum pain area for 10 min once a day and then removed.

[0197] 2) For each group, 15 volunteers who experienced sensitive teeth or gum pain were asked to use for 1 week and then survey was conducted according 5-point Likert scale.

[0198] 3) Scale criteria

[0199] 5: Sensitive teeth or gum pain relief effect lasted for one month in all attached sensitive teeth or gum pain areas.

[0200] 4: Sensitive teeth or gum pain relief effect was definitely felt in all attached sensitive teeth or gum pain areas.

[0201] 3: Sensitive teeth or gum pain relief effect was definitely felt in at least one attached sensitive teeth or gum pain area.

[0202] 2: Sensitive teeth against cold food was felt less sensitive, or gum pain was felt reduced, compared to before use.

[0203] 1: Sensitive teeth or gum pain relief effect was not felt.

[0204] 4. Survey for Feeling of Whitening Effect to Human Subject

[0205] 1) Test subject and instructions: Examples 1 and 4 and Comparative Example 2 were attached to six teeth in the middle of the upper teeth for 30 min or longer once a day and then removed.

[0206] 2) For each group, 15 volunteers who felt the need for tooth whitening because they usually thinks that their teeth are yellow were asked to use for 1 week. Then, survey for feeling of whitening effect, compared to the unattached lower teeth, was conducted according 5-point Likert scale.

[0207] 3) Scale criteria

[0208] 5: Compared to the unattached lower teeth, felt a definite whitening effect than before use within 5 days.

[0209] 4: Compared to the unattached lower teeth, felt that the teeth are definitely brighter than before use within 5 days.

[0210] 3: Compared to the unattached lower teeth, felt that the teeth are definitely brighter than before use after 1 week use.

[0211] 2: Compared to the unattached lower teeth, felt that the teeth are slightly brighter than before use.

[0212] 1: Felt no difference, compared to before use.

[0213] 5. Measurement Result

[0214] The following Table 10 shows removability and adhesive force of Comparative Examples and Examples, and sensitive teeth relieving effect, gingivitis relieving effect and degree of feeling of whitening were listed in table.

TABLE-US-00010 TABLE 10 Comp. Comp. Comp. Exam. Exam. Exam. Exam. Exam. Exam. 4 5 6 5 6 7 Removability 5 5 5 5 5 5 (peel-off) (brush-off) (brush-off) (peel-off) (peel-off) (peel-off) Adhesive 5 5 5 5 5 5 force Sensitive 4 — — 2 — — teeth relieving effect Gingivitis — 5 — — 2 — relieving effect Feeling of — — 4 — — 1 whitening effect

[0215] [Drug Release Rate Comparison Test]

[0216] A) Manipulation

[0217] 0.9% Sodium chloride solution 500 mL is poured in a test tube and a temperature of a test solution is maintained at 32±0.5° C. during drug release test. Example or Comparative Example as a sample is fixed on the upper side of a disk which can be used as a sinker without absorbing, interfering or reacting so that a target attachment surface faces outward. Then, the disk is placed in the test tube with the sample-attached side facing up, and drug release time is calculated from this point of time. The sample-attached disk is aligned parallel to the bottom of the test tube and a paddle blade. Distance between the paddle blade and the sample surface is set to 25±2 mm, and revolutions per min (rpm) is set to 25. At the time of sampling, 100 mL of sample solution is collected at a fixed position (a position 1 cm away from the wall of the test tube, between the top of the paddle blade and the test liquid surface) 30 min after the start of the test. The drug release test was conducted under a general laboratory condition, i.e., under a condition of relative humidity of about 65%, 25° C.

[0218] B) Drug Analysis Method

[0219] Depending on the drug or the content, an appropriate analysis is selected. For example, peroxides are analyzed by titration, metal salts are analyzed by ICP analysis, and natural extracts are analyzed by HPLC.

[0220] C) Result of Medicinal Ingredient Release Test

TABLE-US-00011 TABLE 11 Comp. Comp. Comp. Exam. Exam. Exam. Exam. Exam. Exam. 4 5 6 5 6 7 Time for 10 min 10 min 10 min Undetectable Undetectable Undetectable releasing 70% or more of medicinal ingredient

[0221] As can be seen from Table 11, it was confirmed that Examples could release about 70% of the medicinal ingredient at the time after 10 min from the attachment. However, in the case of Comparative Examples, drug release was not smooth due to rapidly increased hardness, and due to this, the degree of drug release was undetectable.

[0222] [Preparation of Oral Preparation]

[0223] Oral preparations of Examples and Comparative Examples having the following composition were manufactured or purchased.

TABLE-US-00012 TABLE 12 Example 7 Example 8 Example 9 Composition Vitamin E 0.1% Hydrogen peroxide 6% Oxalic acid 6% Magnoliae Cortex extract 0.05% Glyceryl monostearate 30% Glyceryl monolinoleate 40% Glyceryl monooleate 41.5% Ethyl cellulose 10% Butyl ester of 8% Ethyl cellulose 8% ethanol to 100% PVM/MA copolymer(50%) ethanol to 100% ethanol to 100% Comparative Example 8 Comparative Example 9 Comparative Example 10 Composition Vitamin E 0.1% Hydrogen peroxide 6% Oxalic acid 2% Magnoliae Cortex extract 0.05% Glyceryl monostearate 30% Butyl ester of 8% Glyceryl monooleate 41.5% Polyvinyl pyrrolidone 2% PVM/MA copolymer(50%) ethanol to 100% ethanol to 100% ethanol to 100%

[0224] Comparative Example 11: Parodontax™

[0225] Comparative Example 12: Median intensive whitening gel (polyvinyl pyrrolidone, ethanol, water etc.)

[0226] Comparative Example 13: P&G Sensi Stop™

[0227] Examples and Comparative Examples of Table 12 were manufactured according to the following method.

[0228] Ethanol solvent was heated to around 50° C. and then polymers were dissolved therein by stirring with a mechanical stirrer to aid dispersion and dissolution of the polymers at a constant rpm. In particular, the polymer that is contained in a large amount and takes a long time to dissolve (for example, Glyceryl monooleate) was dissolved first and then other polymers were dissolved. Then, other ingredients and a medicinal ingredient were added thereto to make uniform solution or gel.

[0229] <Evaluation of Dissolution Rate and Remaining Amount>

[0230] 1. Evaluation of solubility in hot and humid oral condition without any separate physical force

[0231] In order to evaluate retention time in hot and humid oral condition, an artificial teeth made from a hydroxyapatite table (1 cm diameter) was fixed with silicone molding, and then 0.5 g of each of Examples 7 to 9 and Comparative Examples 8 to 12 was loaded thereon. Then, the time of complete dissolution when immersed in a thermohygrostat of 37° C. and 95% humidity was measured. A separate dissolution test was not carried out to Comparative Example 13 in the form of a patch.

[0232] 2. Evaluation of solubility in artificial saliva with applied physical force like flowing saliva

[0233] An artificial teeth made from a hydroxyapatite table (1 cm diameter) was fixed with silicone molding, and then 1 g of each of Examples 7 to 9 and Comparative Examples 8 to 12 was loaded thereon. Then, in order to evaluate retention time by saliva, the time of complete dissolution when flowing the artificial saliva from top to bottom at a rate of 1 ml/min was measured.

[0234] 3. Test result

[0235] The results of evaluation of solubility in a hot and humid condition without a separate physical force and the results of evaluation of solubility in artificial saliva in which physical force like flowing saliva was applied were shown in the following Table 13.

TABLE-US-00013 TABLE 13 Comp. Comp. Comp. Comp. Comp. Complete dissolution Exam. Exam. Exam. Exam. Exam. Exam. Exam. Exam. (disintegration) time 7 8 9 8 9 10 11 12 Left in condition of >30 min >30 min >30 min <6 min <5 min <5 min 3 min 2 min 37° C., 95% Condition in which >30 min >30 min >30 min 15 min 10 min 15 min 2 min 1 min artificial saliva flows at a rate of 1 ml/min

[0236] As can be seen from Table 13, it was confirmed that Example was not completely dissolved even after 30 min. However, it was confirmed from the results that Comparative Example was easily and completely dissolved.

[0237] <Panel Evaluation>

[0238] 1. Survey for Clinical Sensitive Teeth or Gum Pain Relief

[0239] 1) Test subject and instructions: Examples 7 and 9 and Comparative Examples 8 and 10 to 12 were applied or attached to sensitive teeth or gum pain area for 10 min once a day and then removed.

[0240] 2) For each group, 15 volunteers who experienced sensitive teeth or gum pain were asked to use for 1 week and then survey was conducted according 5-point Likert scale.

[0241] 3) Scale criteria

[0242] 5: Pain relief effect lasted for one month in all sensitive teeth or gum pain areas where the product was applied.

[0243] 4: Pain relief effect was definitely felt in all sensitive teeth or gum pain areas where the product was applied.

[0244] 3: Pain relief effect was definitely felt in at least one sensitive teeth or gum pain areas where the product was applied.

[0245] 2: Sensitive teeth against cold food was felt less sensitive, or gum pain was felt reduced, compared to before use.

[0246] 1: Sensitive teeth or gum pain relief effect was not felt.

[0247] 2. Survey for Feeling of Whitening Effect to Human Subject

[0248] 1) Test subject and instructions: Example 8 and Comparative Examples 9 and 12 were attached to six teeth in the middle of the upper teeth for 30 min or longer once a day and then removed.

[0249] 2) For each group, 15 volunteers who felt the need for tooth whitening because they usually thinks that their teeth are yellow were asked to use for 1 week. Then, survey for feeling of whitening effect, compared to the unattached lower teeth, was conducted according 5-point Likert scale.

[0250] 3) Scale criteria

[0251] 5: Compared to the unattached lower teeth, felt a definite whitening effect than before use within 5 days.

[0252] 4: Compared to the unattached lower teeth, felt that the teeth are definitely brighter than before use within 5 days.

[0253] 3: Compared to the unattached lower teeth, felt that the teeth are definitely brighter than before use after 1 week use.

[0254] 2: Compared to the unattached lower teeth, felt that the teeth are slightly brighter than before use.

[0255] 1: Felt no difference, compared to before use

[0256] 3. Evaluation Result

TABLE-US-00014 TABLE 14 Comp. Comp. Comp. Comp. Comp. Comp. Exam. Exam. Exam. Exam. Exam. Exam. Exam. Exam. Exam. 7 8 9 8 9 10 11 12 13 Sensitive teeth 5 3 3 improvement Whitening 4.5 3 2 effect Gingivitis 4 2 2 improvement

[0257] As can be seen from Table 14, the preparations having composition of Examples of the present invention can have excellent efficacy by facilitating delivery of a medicinal ingredient and securing sufficient attachment time.

INDUSTRIAL APPLICABILITY

[0258] The present invention can be provided as an oral preparation which can be attached to teeth or tooth peripheries and the deliver a medicinal ingredient into the oral cavity. The preparation of the present invention is for attaching to teeth or tooth peripheries with excellent adhesive force.