Tooth-attachable patch capable of being removed by tooth brushing

Abstract

The present invention provides a patch for attaching to teeth or a surrounding part of teeth, and the patch can be easily removed by tooth brushing alone.

Claims

1. A patch for attaching to teeth or a surrounding part of teeth, comprising: a drug layer including a drug component; and a backing layer which is positioned on one side of the drug layer and whose tensile strength is reduced by 50% or more by absorbing moisture, compared to before moisture absorption, wherein the backing layer is capable of being degraded, dispersed into particles and detached by tooth brushing, and wherein a breakable portion is formed on the backing layer.

2. The patch of claim 1, wherein a tensile strength of the backing layer of the patch, which is measured in a state that moisture is sufficiently absorbed so that the moisture content rate does not change for 10 sec, and measured at an environment of temperature of 25° C. using Zwick, DE/1494 universal testing machine at a rate of 0.1 mm/s, is reduced by 50% or more, compared to before moisture absorption.

3. The patch of claim 1, wherein the backing layer has a tensile strength reduction rate of 60% to 95%, compared to before moisture absorption.

4. The patch of claim 1, wherein the backing layer of the patch includes a water-soluble polymer and a water-insoluble polymer.

5. The patch of claim 4, wherein a weight ratio of the water-soluble polymer and the water-insoluble polymer included in the backing layer (water-soluble polymer:water-insoluble polymer) is 1:4 to 4:1.

6. The patch of claim 1, wherein the backing layer includes both of: at least one water-insoluble polymer selected from the group consisting of cellulose acetate phthalate, shellac, polyvinyl acetate, ethyl cellulose, polymethyl methacrylate, methacryloyl ethyl betaine/methacrylate copolymer, methacrylic acid copolymer and aminoalkyl methacrylate copolymer; and at least one water-soluble polymer selected from the group consisting of polyalkyl vinyl ether-maleic acid copolymer (PVM/MA copolymer), polyvinyl alcohol, polyacrylic acid, Poloxamer 407, polyethyleneoxide (Polyox), polyvinyl pyrrolidone-vinyl acetate copolymer (PVP/VA copolymer), polyvinyl pyrrolidone (PVP), polyquaternium-11, polyquaternium-39, carboxypolymethylene (Carbomer), hydroxypropyl methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, gelatin and sodium alginate.

7. The patch of claim 1, wherein the drug layer comprises an ingredient for whitening teeth, an ingredient for preventing or improving sensitive teeth, an ingredient for preventing cavities, or an ingredient for preventing periodontal disease.

8. The patch of claim 1, wherein the breakable portion includes prominence and depression or bubbles.

9. A patch for attaching to teeth or a surrounding part of teeth, comprising: a drug layer attached to teeth or a surrounding part of teeth; and a backing layer which is positioned on one side of the drug layer, wherein the backing layer has a static contact angle which varies over time, and a breakable portion is formed on the backing layer, and wherein the backing layer is capable of being degraded by tooth brushing, and dispersed into particles.

10. The patch of claim 9, wherein the static contact angle varies from 13° to 50° over 10 sec to 300 sec when measured at a temperature of 20° C.

11. The patch of claim 9, wherein the backing layer includes a water-soluble polymer and a water-insoluble polymer.

12. The patch of claim 9, wherein the breakable portion includes prominence and depression or bubbles.

13. A patch for attaching to teeth or a surrounding part of teeth, comprising: a drug layer in contact with teeth or a surrounding part of teeth; and a backing layer positioned on one side of the drug layer, wherein the backing layer includes a polymer having solubility parameter (δ1) of 5 (MPa)½ to 22 (MPa)½; and a polymer having solubility parameter (δ2) of 23.5 (MPa)½ to 40 (MPa)½, wherein the polymer having solubility parameter (δ1) of 5 (MPa)½ to 22 (MPa)½ is any one selected from the group consisting of cellulose acetate phthalate, shellac, polyvinyl acetate, ethyl cellulose, polymethyl methacrylate, methacryloyl ethyl betaine/methacrylate copolymer, methacrylic acid copolymer, aminoalkyl methacrylate copolymer and a mixture thereof, wherein the backing layer is capable of being degraded, dispersed into particles and detached by tooth brushing, and wherein a breakable portion is formed on the backing layer.

14. The patch of claim 13, wherein the polymer having solubility parameter (δ2) of 23.5 (MPa)½ to 40 (MPa)½ is any one selected from the group consisting of polyalkyl vinyl ether-maleic acid copolymer, polyvinyl alcohol, polyacrylic acid, Poloxamer, polyethyleneoxide, polyvinyl pyrrolidone-vinyl acetate copolymer, polyvinyl pyrrolidone, polyquaternium-11, polyquaternium-39, carboxypolymethylene, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, gelatin, sodium alginate and a mixture thereof.

15. The patch of claim 13, wherein a weight ratio of the polymer having solubility parameter (δ1) of 5 (MPa)½ to 22 (MPa)½ and the polymer having solubility parameter (δ2) of 23.5 (MPa)½ to 40 (MPa)½ included in the backing layer is 1:0.2 to 4.0.

16. The patch of claim 13, wherein the backing layer includes a water-soluble polymer and water-insoluble polymer.

17. The patch of claim 13, wherein the breakable portion includes prominence and depression or bubbles.

Description

DESCRIPTION OF DRAWINGS

(1) Other objects and aspects of the present invention will become apparent from the following descriptions of the embodiments with reference to the accompanying drawings in which:

(2) The accompanying drawings illustrate a preferred embodiment of the present invention and together with the foregoing disclosure, serve to provide further understanding of the technical spirit of the present invention, and thus, the present invention is not construed as being limited to the drawing.

(3) FIG. 1 is a graph showing survey response score as the result of evaluating removability of the patches of Comparative Example 1 and Examples 1 to 4 of the present invention.

(4) FIG. 2 is a drawing prefiguratively showing the tooth-attachable patch 1 of the present invention. As prefiguratively shown in FIG. 2a, the patch may include a drug layer 10 and a backing layer 20, and as shown in FIG. 2b, the patch may include another layer separately between the drug layer 10 and the backing layer 20 depending on its purpose.

(5) FIG. 3 is a graph showing the result of evaluating removability of the patches of Comparative Example 3 and Examples 5 to 8 of the present invention.

(6) FIG. 4 is a graph showing the result of evaluating removability of the patches of Comparative Example 5 and Examples 9 to 12 of the present invention.

(7) FIG. 5 is a graph showing the result of evaluating removability of the patches of Comparative Example 7 and Examples 13 and 14.

(8) FIG. 6 is a drawing prefiguratively showing an example of the patch 1 including the breakable portion 30 of the present invention.

(9) FIG. 7 is a drawing prefiguratively showing an example that the breakable portion 30 includes prominence and depression 31 in the patch 1 including the breakable portion 30 of the present invention.

(10) FIG. 8 is a drawing prefiguratively showing an example that the breakable portion 30 includes a bubble 32 in the patch 1 including the breakable portion 30 of the present invention.

BEST MODE

(11) Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. Prior to the description, it should be understood that the terms used in the specification and the appended claims should not be construed as limited to general and dictionary meanings, but interpreted based on the meanings and concepts corresponding to technical aspects of the present invention on the basis of the principle that the inventor is allowed to define terms appropriately for the best explanation. Therefore, the description proposed herein is just a preferable example for the purpose of illustrations only, not intended to limit the scope of the disclosure, so it should be understood that other equivalents and modifications could be made thereto without departing from the scope of the disclosure.

MODE FOR DISCLOSURE

Preparative Example 1

(12) <Preparation of Patch for Tooth Whitening>

(13) Patches for tooth whitening of Comparative Examples having composition of the following Table 1 and Patches for tooth whitening of Examples having composition of the following Table 2 were prepared. % refers to wt %.

(14) TABLE-US-00001 TABLE 1 Comparative Example 1 Comparative Example 2 Drug Hydrogen peroxide 2.9% Hydrogen peroxide 2.9% layer Povidone 19.0% Povidone 19.0% Glycerin 3.0% Glycerin 3.0% Pullulan 1.0% Pullulan 1.0% SPAN80 5.0% SPAN80 5.0% Water etc. to 100% Water etc. to 100% Backing Ethyl Cellulose 15.0% Povidone 15.0% layer Castor oil 10.0% glycerin 3.0% Ethanol etc. to 100% Pullulan 1.0% Water etc. to 100%

(15) TABLE-US-00002 TABLE 2 Example 1 Example 2 Example 3 Example 4 Drug Hydrogen 2.9% Hydrogen 2.9% Hydrogen 2.9% Hydrogen 2.9% layer peroxide peroxide peroxide peroxide Povidone 19.0%  Povidone 19.0%  Povidone 19.0%  Povidone 19.0%  Glycerin 3.0% Glycerin 3.0% Glycerin 3.0% Glycerin 3.0% Pullulan 1.0% Pullulan 1.0% Pullulan 1.0% Pullulan 1.0% SPAN80 5.0% SPAN80 5.0% SPAN80 5.0% SPAN80 5.0% Water etc. to 100% Water etc. to 100% Water etc. to 100% Water etc. to 100% Backing Ethyl Cellulose 12.0%  Ethyl Cellulose 3.0% Ethyl Cellulose 12.0%  Ethyl Cellulose 3.0% layer Hydroxypropyl 3.0% Hydroxypropyl 12.0%  Povidone 3.0% Povidone 12.0%  methylcellulose methylcellulose Castor oil 15.0%  Castor oil 5.0% Castor oil 15.0%  Castor oil 5.0% SPAN80 5.0% SPAN80 15.0%  SPAN80 5.0% SPAN80 15.0%  Ethanol etc. to 100% Ethanol etc. to 100% Ethanol etc. to 100% Ethanol etc. to 100%

(16) Comparative Example 1 of Table 1 is composition for manufacturing a tooth-attachable whitening patch which includes a common water-insoluble supporting material in a backing layer but does not include a water-soluble polymer, and Comparative Example 2 is composition for manufacturing a tooth-attachable whitening patch which only includes a water-soluble polymer in a backing layer.

(17) Patches for tooth whitening having composition of Table 1 and Table 2 were prepared according to the method for preparing a backing layer and a drug reservoir layer in Preparative Example 1 of Korean Patent No. 10-0816250.

(18) <Release Test>

(19) A) Manipulation

(20) 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. The tooth whitening patch is fixed on the upper side of a disk which can be used as a sinker without absorbing, interfering or reacting with a double-sided tape so that a tooth 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 minute (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.

(21) B) Amount Measurement

(22) a. Reagents

(23) —Ammonium Molybdate Solution

(24) Ammonium molybdate 5.3 g is added to water and adjusted to 50 mL.

(25) —Sodium Thiosulfate Solution

(26) Sodium thiosulfate (pentahydrate) 12.41 g is precisely measured, dissolved in water and adjusted to 1 L to make 0.005 N sodium thiosulfate solution.

(27) b. Method for Measuring Concentration 6 N—HCl 5 mL, potassium iodide about 2 g and 1 drop of ammonium molybdate solution are added to 100 mL of the sample collected from the release test and left in the dark for about 10 min. Starch indicator 3 mL is added thereto and released iodine is titrated with 0.005 N sodium thiosulfate solution.

(28) 0.005 N Sodium thiosulfate solution 1 mL=0.08505 mg H.sub.2O.sub.2

(29) C) Result

(30) Release rate is calculated by comparing the amount of hydrogen peroxide in the entire product with the amount of hydrogen peroxide calculated through the release test.

(31) TABLE-US-00003 TABLE 3 Comparative Comparative Example Example Example Example Example Example 1 2 1 2 3 4 Release 86.5 85.9 87.1 85.7 86.8 85.4 rate (%)

(32) As can be seen from Table 3, it can be found that the tooth-attachable patches of Examples 1 to 4 have similar hydrogen peroxide release rate to the patch of Comparative Example 1 not containing a water-soluble polymer in a backing layer and the patch of Comparative Example 2 not containing a water-insoluble polymer, respectively.

(33) <Reverse Release Test>

(34) A) Manipulation

(35) 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. The tooth whitening patch is fixed on the upper side of a disk which can be used as a sinker without absorbing, interfering or reacting with a double-sided tape so that a tooth attachment surface faces to the disk. 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 minute (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.

(36) B) Amount Measurement

(37) a. Reagents

(38) —Ammonium Molybdate Solution

(39) Ammonium molybdate 5.3 g is added to water and adjusted to 50 mL.

(40) —Sodium Thiosulfate Solution

(41) Sodium thiosulfate (pentahydrate) 12.41 g is precisely measured, dissolved in water and adjusted to 1 L to make 0.005 N sodium thiosulfate solution.

(42) b. Method for Measuring Concentration 6 N—HCl 5 mL, potassium iodide about 2 g and 1 drop of ammonium molybdate solution are added to 100 mL of the sample collected from the release test and left in the dark for about 10 min. Starch indicator 3 mL is added thereto and released iodine is titrated with 0.005 N sodium thiosulfate solution.

(43) 0.005 N Sodium thiosulfate solution 1 mL=0.8505 mg H.sub.2O.sub.2

(44) C) Result

(45) Release rate is calculated by comparing the amount of hydrogen peroxide in the entire product with the amount of hydrogen peroxide calculated through the release test.

(46) TABLE-US-00004 TABLE 4 Comparative Comparative Example Example Example Example Example Example 1 2 1 2 3 4 Reverse 3.2 82.8 3.3 3.8 3.5 3.7 release rate (%)

(47) Table 4 shows the reverse release rate of the drug after attaching the sample to the opposite side of the tooth attachment surface, and it is the result of confirming the amount of hydrogen peroxide released through a backing layer.

(48) As can be seen from Table 4, it can be found that in the case of the patch of Comparative Example 1 not containing a water-soluble polymer in a backing layer, the ingredient for whitening teeth contained in a drug layer was not released through the backing layer, but in the case of Comparative Example 2, the drug in a drug layer was released through the backing layer.

(49) Further, it was confirmed that the patches of Examples 1 to 4 have similar reverse release rate to the patch of Comparative Example 1. Through this result, it can be found that the patches of Examples 1 to 4 are well suited to serve as a backing layer of a tooth-attachable patch.

(50) <Survey for Removability>

(51) Survey for removal convenience was conducted to the patches of Comparative Example 1 and Examples 1 to 4 which need a removal process after use, except the patch of Comparative Example 2 which melts away during use. Each of the patches of Comparative Example 1 and Examples 1 to 4 was attached to 30 responders for 15 min according to the group, and then the patch of Comparative Example 1 or Examples 1 to 4 was removed by tooth brushing. Then, each group changed the products and then responded to a questionnaire for removal convenience.

(52) —Criteria for Survey Response—

(53) 5: Removal is very convenient and there is no residue on teeth.

(54) 4: Removal is convenient but there is little residue.

(55) 3: Removal is inconvenient and there is inconvenience due to residue.

(56) 2: Removal is inconvenient and there are many residues.

(57) 1: Removal is very inconvenient and there are so many residues.

(58) As can be seen from FIG. 1, it can be found that the possibility of a role as a backing layer is similar between those of Comparative Example 1 and Examples 1 to 4, but the patch of Example 1 is difficult to be removed only by tooth brushing.

(59) The patches of Examples 1 to 4 were rated excellent in the removability evaluation, and the users evaluated that the patches generally can be easily removed by tooth brushing after use.

(60) <Evaluation of Tensile Strength>

(61) Evaluation apparatus: ZWICK universal testing machine (Zwick, DE/1494)

(62) Evaluation method: Patches of Comparative Examples 1 and 2 and Examples 1 to 4 were cut into 1 cm×7 cm, set in a jig for measuring tensile strength, and tensile strength was measured at a rate of 0.1 mm/s. Patches of the same size were set again in the jig and wetted with enough amount of water not to flow through the center. After 1 min, tensile strength was measured at a room temperature and 50% relative humidity, and compared with the value measured before moisture contact. Moisture content rate for about 10 sec of the patch wetted with enough moisture was changed little.

(63) TABLE-US-00005 TABLE 5 Comparative Comparative Example Example Example Example Example Example 1 2 1 2 3 4 Tensile −0.8 Unable to −65.6 −91.3 −67.9 −93.3 strength measure change rate (%) (−): Indicated by − because tensile strength is reduced compared to before water absorption.

(64) As can be seen from Table 5, it was confirmed that Examples 2 and 4 had the highest tensile strength change rate, Examples 1 and 3 had lower tensile strength change rate than Examples 2 and 4, but generally had a higher change rate.

(65) Through this result, it can be found that tensile strength change and removal of the patch attached to teeth were related to each other. In particular, Examples 2 and 4 having high tensile strength change rate showed excellent removability.

(66) <Evaluation of Degradation by Tooth Brushing>

(67) Two sets of Comparative Example 1 and Examples 1 to 4 were prepared. Each patch of one set was shaken in distilled water for 30 min to leave only a backing layer, dried and then weight of the patch was measured. Each patch of the other set was attached to a slide glass, stored in 37° C., 85% humidity environment for 30 min, and then brushed for 3 min using a brushing machine at a rate of 90 times per min back and forth at a load of 250 g. Then, the slide glass, the brushing chamber and the toothbrush were separated, and washed with distilled water while collecting the washing solution. The collected washing solution was filtered through a 1 mm-mesh sieve, and residue was dried and weighed to check a ratio of the residue based on the total weight of the backing layer.

(68) As a result, it was confirmed that the patch of Comparative Example 1 has a residue ratio of 98% or more, but in the case of the patches of Examples 1 to 4, in which tensile strength was increased by 50% or more compared to before moisture absorption, dry weight of the residue obtained after filtering through a 1 mm-mesh sieve was less than 5%. It was confirmed that the present invention having excellent tensile strength change rate can be easily degraded and removed by tooth brushing.

Preparative Example 2

(69) <Preparation of Patch for Tooth Whitening>

(70) Patches for tooth whitening of Comparative Examples 3 and 4 having composition of the following Table 6 and patches for tooth whitening of Examples 5 to 8 having composition of the following Table 7 were prepared.

(71) TABLE-US-00006 TABLE 6 Comparative Example 3 Comparative Example 4 Drug Hydrogen peroxide 2.9% Hydrogen peroxide 2.9% layer Povidone 19.0% Povidone 19.0% Glycerin 3.0% Glycerin 3.0% Pullulan 1.0% Pullulan 1.0% SPAN80 5.0% SPAN80 5.0% Water etc. to 100% Water etc. to 100% Backing Ethyl Cellulose 15.0% Povidone 15.0% layer Castor oil 10.0% glycerin 3.0% Ethanol etc. to 100% Pullulan 1.0% Water etc. to 100%

(72) TABLE-US-00007 TABLE 7 Example 5 Example 6 Example 7 Example 8 Drug Hydrogen 2.9% Hydrogen 2.9% Hydrogen 2.9% Hydrogen 2.9% layer peroxide peroxide peroxide peroxide Povidone 19.0%  Povidone 19.0%  Povidone 19.0%  Povidone 19.0%  Glycerin 3.0% Glycerin 3.0% Glycerin 3.0% Glycerin 3.0% Pullulan 1.0% Pullulan 1.0% Pullulan 1.0% Pullulan 1.0% SPAN80 5.0% SPAN80 5.0% SPAN80 5.0% SPAN80 5.0% Water etc. to 100% Water etc. to 100% Water etc. to 100% Water etc. to 100% Backing Ethyl Cellulose 12.0%  Ethyl Cellulose 3.0% Ethyl Cellulose 12.0%  Ethyl Cellulose 3.0% layer Hydroxypropyl 3.0% Hydroxypropyl 12.0%  Povidone 3.0% Povidone 12.0%  methylcellulose methylcellulose Castor oil 15.0%  Castor oil 5.0% Castor oil 15.0%  Castor oil 5.0% SPAN80 5.0% SPAN80 15.0%  SPAN80 5.0% SPAN80 15.0%  Ethanol etc. to 100% Ethanol etc. to 100% Ethanol etc. to 100% Ethanol etc. to 100%

(73) Patches for tooth whitening having composition of Table 6 and Table 7 were prepared according to the method for preparing a backing layer and a drug reservoir layer in Preparative Example 1 of Korean Patent No. 10-0816250.

(74) <Release Test>

(75) A) Manipulation

(76) 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. The tooth whitening patch is fixed on the upper side of a disk which can be used as a sinker without absorbing, interfering or reacting with a double-sided tape so that a tooth 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 minute (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.

(77) B) Amount Measurement

(78) a. Reagents

(79) —Ammonium Molybdate Solution

(80) Ammonium molybdate 5.3 g is added to water and adjusted to 50 mL.

(81) —Sodium Thiosulfate Solution

(82) Sodium thiosulfate (pentahydrate) 12.41 g is precisely measured, dissolved in water and adjusted to 1 L to make 0.005 N sodium thiosulfate solution.

(83) b. Method for Measuring Concentration 6 N—HCl 5 mL, potassium iodide about 2 g and 1 drop of ammonium molybdate solution are added to 100 mL of the sample collected from the release test and left in the dark for about 10 min. Starch indicator 3 mL is added thereto and released iodine is titrated with 0.005 N sodium thiosulfate solution.

(84) 0.005 N Sodium thiosulfate solution 1 mL=0.8505 mg H.sub.2O.sub.2

(85) Release rate is calculated by comparing the amount of hydrogen peroxide in the entire product with the amount of hydrogen peroxide calculated through the release test.

(86) TABLE-US-00008 TABLE 8 Comparative Comparative Example Example Example Example Example Example 3 4 5 6 7 8 Release 85.5 84.8 86.1 85.1 85.6 85.7 rate (%)

(87) As can be seen from Table 8, it can be found that all tooth-attachable patches of Comparative Examples and Examples show similar hydrogen peroxide release rate. Namely, it can be found that release efficiency of the ingredient for whitening teeth of the patch of the present invention has excellent release rate similar to the patch having water-insoluble backing layer and the patch having soluble backing layer.

(88) <Reverse Release Test>

(89) A) Manipulation

(90) 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. The tooth whitening patch is fixed on the upper side of a disk which can be used as a sinker without absorbing, interfering or reacting with a double-sided tape so that a tooth attachment surface faces to the disk. 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 minute (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.

(91) B) Amount Measurement

(92) a. Reagents

(93) —Ammonium Molybdate Solution

(94) Ammonium molybdate 5.3 g is added to water and adjusted to 50 mL.

(95) —Sodium Thiosulfate Solution

(96) Sodium thiosulfate (pentahydrate) 12.41 g is precisely measured, dissolved in water and adjusted to 1 L to make 0.005 N sodium thiosulfate solution.

(97) b. Method for Measuring Concentration 6 N—HCl 5 mL, potassium iodide about 2 g and 1 drop of ammonium molybdate solution are added to 100 mL of the sample collected from the release test and left in the dark for about 10 min. Starch indicator 3 mL is added thereto and released iodine is titrated with 0.005 N sodium thiosulfate solution.

(98) 0.005 N Sodium thiosulfate solution 1 mL=0.8505 mg H.sub.2O.sub.2

(99) Release rate is calculated by comparing the amount of hydrogen peroxide in the entire product with the amount of hydrogen peroxide calculated through the release test.

(100) TABLE-US-00009 TABLE 9 Comparative Comparative Example Example Example Example Example Example 3 4 5 6 7 8 Reverse 3.5 80.8 3.7 3.9 3.1 4.0 release rate (%)

(101) The patch of Comparative Example 4 of Table 9 is a patch including a water-soluble polymer in a backing layer. The patch of Comparative Example 4 shows that the hydrogen peroxide contained in a drug layer can be released through a backing layer rather than only delivered to the target site. It can be found that the patches of Comparative Example 3 and Examples 5 to 8 have very low reverse release rate. This shows that the water-insoluble polymer used in the backing layer can block hydrogen peroxide from permeating through the backing layer.

(102) <Survey for Removability>

(103) Survey for removal convenience was conducted to patches of Comparative Example 3 and Examples 5 to 8 which need a removal process after use, except a patch of Comparative Example 4 which melts away during use. Each of the patches of Comparative Example 3 and Examples 5 to 8 was attached to 30 responders for 15 min according to the group, and then the patch of Comparative Example 3 or Examples 5 to 8 was removed by tooth brushing. Then, each group changed the products and then responded to a questionnaire for removal convenience.

(104) —Criteria for Survey Response—

(105) 5: Removal is very convenient and there is no residue on teeth.

(106) 4: Removal is convenient but there is little residue.

(107) 3: Removal is inconvenient and there is inconvenience due to residue.

(108) 2: Removal is inconvenient and there are many residues.

(109) 1: Removal is very inconvenient and there are so many residues.

(110) As can be seen from FIG. 3, when the user brushed teeth at 15 min after attaching the patch of Comparative Example 3, it was evaluated that removal was generally inconvenient and there were residues.

(111) However, the patches of Examples 5 to 8 mostly got 4 points or more, and most of them were evaluated that removal was convenient.

(112) It was confirmed that all patches of Comparative Example 3 and Examples 5 to 8 show an excellent effect on controlling reverse release of the hydrogen peroxide contained in a drug layer. However, it was confirmed that unlike the patches of Examples 5 to 8, the patch of Comparative Example 3 is not easily removed by tooth brushing alone after attachment to teeth.

(113) <Evaluation of Contact Angle>

(114) Evaluation apparatus: FM40 Easy Drop (Kruss, Germany)

(115) Evaluation method: Each patch of Comparative Examples 3 and 4 or Examples 5 to 8 was cut into 1 cm×3 cm, put on a testing bench of an apparatus, and then 5 μl of water was dropped thereon. Then contact angle from 10 sec to 300 sec was measured at a room temperature (about 20° C.) under typical laboratory conditions, and variation was calculated.

(116) TABLE-US-00010 TABLE 10 Comparative Comparative Example Example Example Example Example Example 3 4 5 6 7 8 Static contact 1.2 Unable to 15.1 40.5 17.7 43.6 angle measure variation (°)

(117) As can be seen form Table 10, it can be found that contact angle variation of the patches of Examples 5 to 8 is 10 times or more than that of the patch of Comparative Example 3.

(118) In particular, it was found that the patches of Examples 5 to 8 have excellent removability by tooth brushing, and this is thought to be the influence by the contact angle variation of Table 10.

Preparative Example 3

(119) <Preparation of Patch for Tooth Whitening>

(120) Patches for tooth whitening of Comparative Examples 5 and 6 having composition of the following Table 11 and patches for tooth whitening of Examples 9 to 12 having composition of the following Table 12 were prepared.

(121) TABLE-US-00011 TABLE 11 Comparative Example 5 Comparative Example 6 Drug Hydrogen peroxide 2.9% Hydrogen peroxide 2.9% layer Povidone 19.0% Povidone 19.0% Glycerin 3.0% Glycerin 3.0% Pullulan 1.0% Pullulan 1.0% SPAN80 5.0% SPAN80 5.0% Water etc. to 100% Water etc. to 100% Backing Ethyl Cellulose 15.0% Povidone 15.0% layer Castor oil 10.0% glycerin 3.0% Ethanol etc. to 100% Pullulan 1.0% Water etc. to 100%

(122) TABLE-US-00012 TABLE 12 Example 9 Example 10 Example 11 Example 12 Drug Hydrogen 2.9% Hydrogen 2.9% Hydrogen 2.9% Hydrogen 2.9% layer peroxide peroxide peroxide peroxide Povidone 19.0%  Povidone 19.0%  Povidone 19.0%  Povidone 19.0%  Glycerin 3.0% Glycerin 3.0% Glycerin 3.0% Glycerin 3.0% Pullulan 1.0% Pullulan 1.0% Pullulan 1.0% Pullulan 1.0% SPAN80 5.0% SPAN80 5.0% SPAN80 5.0% SPAN80 5.0% Water etc. to 100% Water etc. to 100% Water etc. to 100% Water etc. to 100% Backing Ethyl Cellulose 12.0%  Ethyl Cellulose 3.0% Ethyl Cellulose 12.0%  Ethyl Cellulose 3.0% layer Hydroxypropyl 3.0% Hydroxypropyl 12.0%  Povidone 3.0% Povidone 12.0%  methylcellulose 2910 methylcellulose 2910 Castor oil 15.0%  Castor oil 5.0% Castor oil 15.0%  Castor oil 5.0% SPAN80 5.0% SPAN80 15.0%  SPAN80 5.0% SPAN80 15.0%  Ethanol etc. to 100% Ethanol etc. to 100% Ethanol etc. to 100% Ethanol etc. to 100%

(123) Patches for tooth whitening having composition of Table 11 and Table 12 were prepared according to the method for preparing a backing layer and a drug reservoir layer in Preparative Example 1 of Korean Patent No. 10-0816250.

(124) Solubility parameter of each polymer for forming a backing layer contained in the backing layer of Examples 9 to 12 is as follows. Ethyl cellulose: 20.6 HPMC (Hydroxypropyl methylcellulose) 2910:30 PVP (Polyvinylpyrrolidone): 24.9

(125) <Release Test>

(126) A) Manipulation

(127) 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. The tooth whitening patch is fixed on the upper side of a disk which can be used as a sinker without absorbing, interfering or reacting with a double-sided tape so that a tooth 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 minute (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.

(128) B) Amount Measurement

(129) a. Reagents

(130) —Ammonium Molybdate Solution

(131) Ammonium molybdate 5.3 g is added to water and adjusted to 50 mL.

(132) —Sodium Thiosulfate Solution

(133) Sodium thiosulfate (pentahydrate) 12.41 g is precisely measured, dissolved in water and adjusted to 1 L to make 0.005 N sodium thiosulfate solution.

(134) b. Method for Measuring Concentration 6 N—HCl 5 mL, potassium iodide about 2 g and 1 drop of ammonium molybdate solution are added to 100 mL of the sample collected from the release test and left in the dark for about 10 min. Starch indicator 3 mL is added thereto and released iodine is titrated with 0.005 N sodium thiosulfate solution.

(135) 0.005 N Sodium thiosulfate solution 1 mL=0.8505 mg H.sub.2O.sub.2

(136) C) Result

(137) Release rate is calculated by comparing the amount of hydrogen peroxide in the entire product with the amount of hydrogen peroxide calculated through the release test, and shown in the following Table 13.

(138) TABLE-US-00013 TABLE 13 Comparative Comparative Example Example Example Example Example Example 5 6 9 10 11 12 Release 85.9 89.7 86.4 84.9 86.8 84.6 rate (wt %)

(139) As can be seen from Table 13, it can be found that all tooth-attachable patches of Comparative Examples and Examples show similar hydrogen peroxide release rate. Namely, it can be found that release efficiency of the ingredient for whitening teeth of the patch of the present invention has excellent release rate similar to the patch having water-insoluble backing layer and the patch having soluble backing layer.

(140) <Reverse Release Test>

(141) A) Manipulation

(142) 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. The tooth whitening patch is fixed on the upper side of a disk which can be used as a sinker without absorbing, interfering or reacting with a double-sided tape so that a tooth attachment surface faces to the disk. 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 minute (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.

(143) B) Amount Measurement

(144) a. Reagents

(145) —Ammonium Molybdate Solution

(146) Ammonium molybdate 5.3 g is added to water and adjusted to 50 mL.

(147) —Sodium Thiosulfate Solution

(148) Sodium thiosulfate (pentahydrate) 12.41 g is precisely measured, dissolved in water and adjusted to 1 L to make 0.005 N sodium thiosulfate solution.

(149) b. Method for Measuring Concentration 6 N—HCl 5 mL, potassium iodide about 2 g and 1 drop of ammonium molybdate solution are added to 100 mL of the sample collected from the release test and left in the dark for about 10 min. Starch indicator 3 mL is added thereto and released iodine is titrated with 0.005 N sodium thiosulfate solution.

(150) 0.005 N Sodium thiosulfate solution 1 mL=0.8505 mg H.sub.2O.sub.2

(151) C) Result

(152) Release rate is calculated by comparing the amount of hydrogen peroxide in the entire product with the amount of hydrogen peroxide calculated through the release test, and shown in the following Table 14.

(153) TABLE-US-00014 TABLE 14 Comparative Comparative Example Example Example Example Example Example 5 6 9 10 11 12 Reverse 3.7 82.7 3.3 3.5 3.1 3.8 release rate (%)

(154) The patch of Comparative Example 6 of Table 14 is a patch including a water-soluble polymer in a backing layer. The patch of Comparative Example 6 shows that the hydrogen peroxide contained in a drug layer can be reversely released through a backing layer thereby also releasing a drug in the opposite direction to teeth rather than only delivered to the target site. It can be found that the patches of Comparative Example 5 and Examples 9 to 12 have very low reverse release rate. This shows that the water-insoluble polymer used in the backing layer can block hydrogen peroxide from permeating through the backing layer.

(155) <Survey for Removability>

(156) Survey for removal convenience was conducted to patches of Comparative Example 5 and Examples 9 to 12 which need a removal process after use, except a patch of Comparative Example 4 which melts away during use. Each of the patches of Comparative Example 5 and Examples 9 to 12 was attached to 30 responders for 15 min according to the group, and then the patch of Comparative Example 5 or Examples 9 to 12 was removed by tooth brushing. Then, each group changed the products and then responded to a questionnaire for removal convenience.

(157) —Criteria for Survey Response—

(158) 5: Removal is very convenient and there is no residue on teeth.

(159) 4: Removal is convenient but there is little residue.

(160) 3: Removal is inconvenient and there is inconvenience due to residue.

(161) 2: Removal is inconvenient and there are many residues.

(162) 1: Removal is very inconvenient and there are so many residues.

(163) As can be seen from FIG. 4, when the user brushed teeth at 15 min after attaching the patch of Comparative Example 5, it was evaluated that removal was generally inconvenient and there were residues.

(164) However, the patches of Examples 9 to 12 mostly got 4 points or more, and most of them were evaluated that removal was convenient.

(165) It was confirmed that all patches of Comparative Example 5 and Examples 9 to 12 show an excellent effect on controlling reverse release of the hydrogen peroxide contained in a drug layer. However, it was confirmed that unlike the patches of Examples 9 to 12, the patch of Comparative Example 5 is not easily removed by tooth brushing alone after attachment to teeth.

Preparative Example 4

(166) <Preparation of Patch for Tooth Whitening>

(167) Patches for tooth whitening having composition of the following Table 15 were prepared.

(168) TABLE-US-00015 TABLE 15 Breakable Comparative Example 7 Example 13 Example 14 portion No Bubble Prominence and depression Drug Hydrogen peroxide 2.9% Hydrogen peroxide 2.9% Hydrogen peroxide 2.9% layer Povidone 19.0%  Povidone 19.0%  Povidone 19.0%  Glycerin 3.0% Glycerin 3.0% Glycerin 3.0% Pullulan 1.0% Pullulan 1.0% Pullulan 1.0% Water etc. to 100% Water etc. to 100% Water etc. to 100% Backing Ethyl Cellulose 20.0%  Ethyl Cellulose 20.0%  Ethyl Cellulose 20.0%  layer Castor oil 10.0%  Castor oil 10.0%  Castor oil 10.0%  Ethanol etc. to 100% Ethanol etc. to 100% Ethanol etc. to 100%

(169) After preparing a patch according to a prescription of the above Table, for Examples, bubbles (Example 13), and prominence and depression (Example 14) were formed on the backing layer or the entire patch.

(170) The prominence and depression was formed by pressing the patch using a grid, and bubbles are artificially formed by using a homo-mixer and the like just prior to application of the backing layer.

(171) The lines constituting the grid have width of 0.1 mm or less and its depth is varied according to the thickness of the patch. After the prominence and depression is formed, the thickness of the concave portion of the patch should be 30 μm or less and the interval between grids should be 1 mm.

(172) Patches for tooth whitening having composition of the Table 15 were prepared according to the method for preparing a backing layer and a drug reservoir layer in Preparative Example 1 of Korean Patent No. 10-0816250.

(173) <Survey for Removal Convenience>

(174) For each group of 30 individuals, 5 groups used in patches of Comparative Example 7 and Examples 13 and 14. Two groups using Comparative Example 7 stripped off the patches after 30 min attachment or removed the patches by tooth brushing. The groups using the patches of Examples 13 and 14 removed the patches by tooth brushing after 30 min attachment. Then, survey for removal convenience was conducted for each group.

(175) —Criteria for Survey Response—

(176) 5: Removal is very convenient and there is no residue.

(177) 4: Removal is convenient but there is little residue.

(178) 3: Removal is inconvenient and there is inconvenience due to residue.

(179) 2: Removal is inconvenient and there are many residues.

(180) 1: Removal is very inconvenient and there are so many residues.

(181) As can be seen from FIG. 5, when the user brushed teeth at 30 min after attaching the patch of Comparative Example 7, it was evaluated that removal was generally inconvenient and there were many residues.

(182) However, the patches of Examples 13 and 14 mostly got 4 points or higher, and most of them were evaluated that removal was convenient.

(183) <Evaluation of Degradation by Tooth Brushing>

(184) Two sets of Comparative Example 7 and Examples 13 and 14 were prepared to the same size. Each patch of one set was shaken in distilled water for 30 min to leave only a backing layer, dried and then weight of the patch was measured. Each patch of the other set was attached to a slide glass, stored in 37° C., 85% humidity environment for 30 min, and then brushed for 3 min using a brushing machine at a rate of 90 times per min back and forth at a load of 250 g. Then, the slide glass, the brushing chamber and the toothbrush were separated, and washed with distilled water while collecting the washing solution. The collected washing solution was filtered through a 1 mm-mesh sieve, and residue was dried and weighed to calculate a ratio of the residue based on the total weight of the backing layer.

(185) TABLE-US-00016 TABLE 16 Comparative Example 7 Example 13 Example 14 Residue ratio 96.8 1.3 1.5 (wt %)

(186) As can be seen from Table 16, it was confirmed that the patch of Comparative Example 7 was hardly degraded by tooth brushing, and could not pass through the 1 mm-mesh sieve. Namely, about 96 wt % or more of the patch was remained on the sieve.

(187) However, the patches of Examples 13 and 14 were remained about 1.3 wt %, 1.5 wt % of dry weight based on initial weight, respectively.

(188) As can be seen from the result, it was confirmed that the patches were easily degraded by the breakable portion form on the patches of Examples 13 and 14, and it was conveniently removed by tooth brushing.

INDUSTRIAL APPLICABILITY

(189) The present invention can provide a patch which can be easily removed by tooth brushing after being attached to teeth or a surrounding part of teeth.

(190) The present invention has been described in detail. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the disclosure, are given by way of illustration only, since various changes and modifications within the scope of the disclosure will become apparent to those skilled in the art from this detailed description.