KR20050082187A - Dry type patches convenient for use - Google Patents

Abstract

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a dry type tooth whitening patch that does not use a tray. In a patch of tooth type enamel adhesion of a matrix type having a drug layer and a support layer, a peroxide as a tooth whitening agent on the drug layer Including a hydrophilic glassy polymer (glassy polymer), when the contact with the teeth, the glass polymer is hydrated, resulting in a strong adhesion and release of the whitening agent, the thickness of the drug layer is characterized in that more than 10 times the thickness of the support layer Tooth whitening patch, including a support layer relatively thin compared to the thickness of the drug layer, because it is excellent in the adhesion and whitening effect to the teeth, and does not need to be removed after attachment, it is not only convenient to use, but also to produce a support layer Productivity is easy because the cost and time can be minimized.

Description

Dry tooth whitening patch for ease of use {DRY TYPE PATCHES CONVENIENT FOR USE}

The present invention is a dry type tooth whitening patch that whitens a tooth only by attaching it to a tooth without using a tray, and includes a support layer relatively thin as compared to the thickness of the drug layer. It is a dry tooth whitening patch that is easy to use because it has excellent adhesion and whitening effect and does not need to be removed after attachment.

Recently, with increasing interest in teeth whitening, a lot of tray products that can see the teeth whitening effect in a short time have been sold. These tray products are largely divided into OTC products and those requiring doctor's prescription. OTC products can be purchased at pharmacies or hypermarkets and are inexpensive, while using trays made of a typical one-size and shape do not fit well to each tooth. Therefore, it is known that irritation by the tray itself or irritation caused by excessive use of the gel applied to the tray, may cause inconveniences as well as inconvenience due to leakage of the gel during use. In addition, in most cases, it is difficult to use during everyday life because it is noticeable to others when it is attached, it is generally used for overnight use. On the other hand, in the latter case, which requires a doctor's prescription, since the personal tray is manufactured with the exact size and shape by measuring the shape or size of the patient's teeth, the same problems as in OTC products occur, but the cost is high. It is a hassle to visit a doctor.

In recent years, many patent applications related to tooth whitening adhesives that do not use a tray have been applied to solve these problems. In 1994 Curtis et al. Disclosed a tooth whitening agent in which US Pat. No. 5,310,563 encapsulates a peroxide or various active ingredients in a substance such as a putty using a silicone polymer. Here, the force that the tooth whitening adhesive adheres to the teeth is caused by the elasticity of the putty material such as rubber, and nothing is specifically mentioned about the shape. However, the tooth whitening adhesive using a substance such as putty has a disadvantage that the whitening effect is relatively low even if it is attached to the teeth for the same time because the peroxide is encapsulated, and because it is only attached to the teeth by elastic force. There is also a problem in that the tongue is attached to a severely curved tooth in the mouth with a lot of movement of the tongue, and if it is irritated, for example, where it is hit by a cough or the like, it is more likely to be separated from the tooth and return to its original shape.

Meanwhile, 3M (3M) is a gel retaining insert (gel) with a microstructure that is being developed and used to further increase the adhesion between the gel and the tooth to a tooth whitening product (Zaris ^R ) using a tray. By applying a retention insert, a patent application for a tooth whitening adhesive using only a gel retention insert without using a tray has been applied. This means that a microporous gel retention insert made of PSA (Pressure Sensitive Adhesive) and a dispersion of tooth whitening ingredients is used as a tooth whitening adhesive. A gel retention insert having a microstructure insoluble in water is applied to the tray. It is not tested whether it will have the same whitening effect as used. That is, since most polymers used in PSA use solvents that cannot be used in oral products, such as methylene chloride and ethyl acetate, rather than water or alcohol, they are not suitable for the formulation directly attached to teeth in the oral cavity. It is considered that there is an inadequate aspect to commercialize acrylic polymers that can be commercialized because of their poor compatibility with peroxides when used as an adhesive for teeth whitening.

Colgate also uses ethylene oxide polymer with thermoplastic properties in U.S. Patent No. 6,419,906 for tooth whitening adhesives and percarbonate as a solid type for whitening agents. Disclosed is an adhesive for whitening teeth, which is characterized by the use of. However, since polyethylene oxide is excellent in compatibility with peroxides but has a disadvantage in that tooth adhesion is inferior, it seems that there is a problem in that the adhesive using the same is inferior in fit.

In particular, P & G commercializes and sells these teeth whitening strips. The tooth whitening strip sold by P & G solves the problem of tray products because the tooth whitening component is applied thinly and uniformly on thin and flexible polyethylene strip without using tray. However, this product is a wet type, and the adhesion between the tooth and the product is not so strong that it is easy to attach and detach, whereas it is severely impacted, such as coughing or laughing loudly while attached to the tooth. If you are impacted by the back, there is a disadvantage that it can not be attached to the desired position for a desired time. This phenomenon is known to occur more in the lower teeth than in the upper teeth. In fact, as seen in P & G's tooth whitening strips, this shape appears to be applied to the lower teeth rather than the upper teeth, which are relatively large in size and smooth in flexion. However, in the case of P & G's tooth whitening strips, even if the trapezoid does not cover the two canine ends, wet adhesion to the teeth is insufficient.

The oral ophthalmic patch disclosed by Ryan Corporation in JP-A-10-17448 (JP 1998-017448) consists of two layers, a support layer and a drug layer. Here, the support layer is prepared by dissolving the used polymer material and plasticizer in an organic solvent, extending it in a plastic or metal batt, removing or drying the organic solvent, or vacuum drying. The thickness of the support layer is 50 to 500. It is mentioned that the thickness is preferably 200 to 300 µm, in view of usability and the like. However, the main polymer of the support layer is water-insoluble polymers such as ethyl cellulose, cellulose acetate, methacrylic acid methacrylate trimethyl ammonium copolymer, polyvinyl acetal, hydroxypropyl Methyl cellulose phthalate (hydroxypropylmethyl cellulose phthalate) according to the above manufacturing method to produce the same thickness as described above is a time-consuming and expensive and slow production speed is difficult to mass production. For example, in the case of vacuum drying, these polymers are insoluble in water, so there is no choice but to use an organic solvent. When making a film of such thickness with an organic solvent, the vacuum drying causes a low heat point and may cause a fire or explosion. In addition, when the coating is applied without the vacuum, and the organic solvent is removed and dried, the adhesive layer may have a similar or more time and cost, thereby producing a product using a vacuum freeze drying method, which takes a lot of production time. In addition, when the thickness of the support layer is set to 50 to 500 µm and 200 to 300 µm, which is preferable in the present invention, there is a trouble of peeling off after use due to the characteristics of the support layer which is insoluble in water. Because the contact time is important for the tooth whitening reaction, most OTC products sold in the US are recommended to be worn twice a day for 30 minutes each time. However, for busy office workers or those who like simplicity, it is cumbersome to keep a certain amount of time at least once a day. Therefore, if you just attach and sleep at night, it will not be more convenient. However, when the thickness of the support layer is 50 to 500 μm, preferably 200 to 300 μm, as in Japanese Patent Application Laid-Open No. Hei 10-17448 (JP 1998-017448), it is undesirably detached and insoluble in water while sticking and sleeping. The support layer may be caught in the throat, and in this case, there may be a risk of asphyxiation.

The formulation disclosed in Korean Patent Application No. 10-2001-0088418 of SK Chemicals is characterized by not having to remove the support layer. In other words, an enteric coating polymer is used here, and since it is dissolved after a certain time by saliva, it does not need to be removed after use. In the thickness part, since skin irritation occurs by the tooth whitening active substance in less than 5 micrometers, it is a characteristic that skin irritation can be prevented when it is 5-150 micrometers. In addition, the melting time of the support layer can be seen to melt within 40 minutes as can be seen in the embodiment. However, when a long time of adhesion is desired for more than 40 minutes, such a formulation using an enteric coating material that dissolves slowly over time due to intraoral conditions is not preferable.

The tooth whitening patch previously developed by the applicant is a dry type tooth whitening agent using a peroxide stabilized hydrophilic glassy polymer as the main polymer of the drug layer. It is a safer formulation in which the glassy polymer is hydrated by moisture, resulting in a strong adhesion and release of the whitening agent. Such dry patches can be attached for a sufficient time and are characterized in that the whitening component does not penetrate into the support layer using a water insoluble and water impermeable support layer. The advantage of dry patches is that when the patch is removed from the release liner and attached to the teeth, the adhesive layer does not remain on the hand even if the adhesive layer is on the hand, and it does not touch the face or the lips accidentally. . In addition, even in view of human safety issues that may be caused by the inclusion of high concentrations of peroxides as whitening agents, dry patches that do not have whitening components on the hands or skin are more preferred.

These tooth-attached whitening patches require removal of the support layer when attached for a period of time and then removed at the desired time. Especially for dry patches with strong adhesion, the support layer must have a certain thickness (typically 50 µm or more). You can maintain shape without tearing when you produce. However, when the patch is manufactured by a casting method, an organic solvent is used in the case of a support layer using a polymer that is insoluble in water, and in the case of a solvent having a low boiling point, unwanted bubbles are generated during the process of increasing the production rate. To increase the defective rate. In order to reduce the occurrence of such bubbles, the drying rate can only be lowered at a low temperature, which may cause a problem of low productivity.

In order to solve this problem, in the present invention, while having a support layer serving as a barrier, the thickness thereof is minimized to increase productivity, and an edible grade used for waterproofing medicine or food, although it is insoluble in water. By using a polymer having the properties or properties to develop a convenient dry type (white type) teeth whitening patch that does not have to be removed after use.

On the other hand, the most influential effect in the whitening of teeth is the concentration of the whitening agent and the contact time. However, if the concentration is high side effects are also high, so there is a limit to increase the effect by adjusting the concentration. According to this principle, representative dental-prescribed at-home bleaching is the main use of 6-8 hours of sleep. However, in order to use during bedtime, there is a problem in that a lot of costs are required for the procedure because it is necessary to manufacture a custom tray for the individual's teeth. Among strip products that do not use a tray, a product in which a gel is applied to a PE film thinly is also inconvenient to wear for 30 minutes or more due to lack of adhesive strength. In addition, even in a dry product that has excellent adhesion and can be attached for a relatively long time, when it has a water-insoluble support layer having a thickness of 50 μm or more, a whitening patch is attached and the patch is separated from the teeth during bedtime, thereby causing unwanted palate or tongue, or There is a risk of getting stuck in the throat.

In view of the above problems, it is necessary to develop a tooth whitening patch that can be used safely, comfortably and conveniently during bedtime. To this end, in the present invention, a strong adhesive force of dryness is employed, but at least a thickness of the support layer is manufactured. In addition, by using a component having an edible grade or property in the support layer, the present invention has been completed.

It is an object of the present invention to minimize the thickness of the support layer in dry type tooth whitening patch, not only to increase productivity, but also more convenient to use, no need to remove after use, safe, comfortable and convenient to use during bedtime To provide a whitening patch that can be.

In order to achieve the above object, in the present invention, in the patch for tooth enamel adhesion of the matrix type having a drug layer and a support layer, the drug layer includes a peroxide and a hydrophilic glassy polymer as a tooth whitening agent. In contact with the tooth, the glass polymer is hydrated to produce a strong adhesive force and the release of the whitening agent is started, and provides a dry type tooth whitening patch, characterized in that the thickness of the drug layer is more than 10 times the thickness of the support layer.

Here, since the support layer does not penetrate the drug layer at all and does not melt at all during use, the support layer may be as thin as 2 to 3 μm, and may have a maximum thickness of 20 to 30 μm to have a thickness that does not have to be removed. It is suitable to have the following thickness. The preferred thickness of the support layer is 10 μm or less, more preferably 5 μm or less. Moreover, the characteristic of a support layer is water impermeability, and it is desirable that it is an edible component or grade.

In the present invention, unlike wet, due to the nature of dry patches, when the support layer is thin or porous, the drug layer is made as thin as possible and adhered to the teeth by using the drug that is not released in the direction of the undesired support layer. The dry tooth whitening patch that allows the support layer to remain intact without degrading itself by pH or time, or dissolving in water or water, while remaining completely insoluble. Developed.

That is, the tooth whitening patch according to the present invention is a dry patch of the matrix type, which contains a peroxide and a peroxide stabilizer as a whitening agent in the adhesion layer, and a hydrophilic glassy polymer is used as the main base polymer, and the tooth whitening agent Furnace containing peroxide and peroxide stabilizer and having an insoluble and impermeable support layer in water, where the support layer is preferably very thin (less than 5 μm) and thus costs in the production of casting or extrusion molding. In addition to being cheap and high in production speed, there is little foreign material and excellent adhesion to teeth, and the insoluble support layer is not left in unwanted parts of the mouth, so it can be used for a long time and even at bedtime.

In order to produce a very thin support layer, it is more preferable to use a gravure coater than a comma coater for coating to produce a uniform film when produced by the casting method. Gravure coating, a coating method mainly used for printing, can be coated with 2 ~ 3 ㎛, and at such a thin thickness, even if the drying conditions are mild, there is no possibility of introducing air bubbles during production and the drying time can be shortened. It is possible to increase the production speed, and thus to lower the production cost.

When the support layer is thin in the tooth whitening patch, the flexibility of the patch is more excellent and the foreign matter is less. In addition, if the support layer is thin, after the drug layer is completely dissolved after sufficient time of attachment, only the invisible thin film of 5 μm or less remains, so there is an advantage in that the convenience of use is improved because it is not removed. This feature makes the patch of the present invention also suitable for use at bedtime. That is, the tooth whitening patch according to the present invention not only has the advantage of less foreign matter and lower cost than using the conventional dental tray overnight, and is thinner than the gel and is stronger than the wet patch without the tray. It can be used for a long time with adhesive force, and it is safer and more convenient than a product having a support layer having a thickness of 9 μm. In the case of bedtime use, it is preferable that the product is adhered to the teeth for 6 to 8 hours while the drug layer has a suitable thickness so that the whitening agent can be released slowly during this time.

The above characteristics of the patch according to the present invention is possible because it is a dry product having a strong tooth adhesion. That is, in the case of wet, if the support layer is too thin, it is not easy enough to bury the skin or mucous membranes even before hydration and to protect the drug layer gel to maintain its shape. On the other hand, when using a hydrophilic glassy polymer (hydrophilic glassy polymer) such as the present invention, not only sticky before hydration, but also lacks adhesion or very weak and does not adhere to the skin or hands, while being hydrated by a small amount of water on the surface of the tooth when used Since strong adhesion and stickiness occurs, even if the support layer is thinner than 5 ㎛ can be used conveniently.

Hereinafter, the configuration of the dry tooth whitening patch according to the present invention will be described in more detail. 1 is a cross-sectional view showing an embodiment of a tooth whitening patch according to the present invention. As shown here, it can be seen that the thickness of the support layer is relatively very thin compared to the thickness of the drug layer.

In the present invention, first, in order to make a dry patch, there is no adhesive strength or a weak adhesive strength in the initial state, while being hydrated by a small amount of water at the site where the whitening agent is desired to act, a strong adhesive force is generated or stronger, and the release of the whitening agent starts. There is a need for a polymer. In the present invention, a hydrophilic glass polymer having such physical properties was used as the main polymer for the patch of matrix form.

In the patch of the present invention, the support layer is a water-insoluble, water-impermeable polymer as a film forming agent, and serves to prevent the patch from being deformed or desorbed by saliva without sticking to the gums or tongue when attaching the teeth.

The tooth whitening patch, pre- filed by the present inventors, is a dry tooth whitening agent using a peroxide stabilized hydrophilic glass polymer as the main polymer of the drug layer, and can be attached for a sufficient time, and is insoluble in water and not permeable to water. The support layer was used to prevent the whitening component from penetrating the support layer. In the case of such patches, in order to remove them at a desired time after attaching them for a certain period of time, the support layer must be detached. In particular, in a dry patch with strong adhesion, the support layer must have a certain thickness (typically 50 μm or more) to prevent tearing. Can be maintained. However, when the patch is produced by a casting method, the support layer using a polymer insoluble in water uses an organic solvent. At this time, a solvent having a low boiling point may generate unwanted bubbles in the process of increasing the production rate, thereby increasing the defect rate. . In particular, the most suitable organic solvent for use in the oral cavity is ethanol, the boiling point of the ethanol boiling point (boiling point) is not easy to dry to more than 60 ℃ to 80 ℃. If the drying temperature is high, because the temperature difference between the contact with the hot air and the bottom portion when drying, bubbles are generated, but to reduce the bubble generation will have to lower the drying speed at a lower temperature, which leads to a decrease in productivity. . However, even if ethanol is used as the solvent, if the thickness of the support layer is thin, it is possible to reduce the bubble generation and to improve the production speed.

The tooth whitening patch according to the present invention is a matrix type patch, which is attached to the enamel layer of the tooth rather than to the skin or mucous membranes and supplies the whitening agent to the tooth surface for a sufficient time, so that the whitening agent is the enamel of the outermost layer of the tooth ( In addition to whitening the coloring material attached to the enamel layer, the whitening component penetrates into the enamel and the dentin of the underlying layer, thereby whitening the teeth. Such a patch of the present invention is attached to the tooth, the principle that can release the whitening agent in the matrix on the surface of the tooth is as follows. Among the methods used for transdermal delivery with time lag in the field of drug delivery, there is an idea of the use of water emanating from the skin as an example of a transdermal formulation that causes the drug to release after a period of time after attachment. In other words, the drug impermeable barrier (barrier) is installed between the skin adhesion surface and the drug reservoir, the drug permeability of the drug over time by using the hydration of the barrier by moisture invading the skin after the formulation is attached Will increase. In this case, the barrier material is a hydrophilic glassy polymer. In the present invention, this technique is used. By using a hydrophilic glass polymer in several layers in a patch of matrix type, the whitening agent is not released during storage or when touched by hand for attachment to a tooth, but is hydrated by moisture on the surface of the tooth. At the beginning, adhesion occurs and release of the whitening agent occurs. Thus, one feature of the patch of the present invention is the use of hydrophilic glass polymers in several layers except for the support layer of the dry patch.

Glass polymers that can be used in the adhesive layer of the matrix type patch according to the present invention include polyalkyl vinyl ether-maleic acid copolymer (PVM / MA copolymer; Gantrez AN 119, AN 139, S-97), polyvinyl alcohol, poly Acrylic acid, poloxamer 407 (Pluronic), polyvinylpyrrolidone-vinylacetate copolymer (PVP / VA copolymer; Luviskol VA, Plasdone S PVP / VA), polyvinylpyrrolidone (PVP, K-15 to K-120), Polyquaternium-11 (Gafquat 755N), Polyquaternium-39 (Merquat plus 3330), Carbomer (Carbopol), hydroxypropylmethyl cellulose, hydroxy Ethyl cellulose, hydroxypropyl cellulose, gelatin, sodium alginate, or mixtures thereof are exemplified. As these solvents, water, ethanol and the mixing ratio thereof can be controlled.

Teeth whitening patches must be flexible enough because they attach directly to the teeth and must be easily shaped as the teeth are bent. Since some of these polymers are inferior in flexibility, a suitable plasticizer may be added. Suitable plasticizers vary depending on the type of polymer and its formulation, but may be generally used polypropylene glycol, glycerin, or polyethylene glycol.

Tooth whitening agents included in the adhesion layer attached to the tooth enamel include hydrogen peroxide, carbamide peroxide, calcium peroxide, sodium percarbonate, sodium perborate, and peroxide. Sodium pyrophosphate peroxidate, and mixtures thereof. Sodium pyrophosphate (TSPP-H ₂ O ₂ ), an addition compound of sodium pyrophosphate and hydrogen peroxide, exhibits the properties of hydrogen peroxide in aqueous solution or crystalline state and exhibits the properties of sodium pyrophosphate itself. Normally, sodium pyrophosphate stabilizes hydrogen peroxide without altering its original properties and prevents the drawbacks of using hydrogen peroxide alone. In other words, hydrogen peroxide is accelerated by metal catalysts, ultraviolet rays, oxidases, heat treatments, etc., but sodium pyrophosphate is stable against these conditions and allows the hydrogen peroxide to exhibit its original properties and properties. In fact, sodium pyrophosphate was more stable at 40 ° C. over time than when only peroxides were used in liquids, gels, and pastes. However, peroxide stability in the patch could not be easily obtained using sodium pyrophosphate as a whitening agent.

Generally, peroxides are difficult to stabilize in a product due to their excellent reactivity, in particular, it is known that they are not compatible with polymers. In-product stabilization of peroxides is related to the shape and formulation of the product, and relatively many peroxide stabilization techniques are disclosed in general gels, pastes, and solutions. It is known that stability can be ensured. However, peroxide stabilization in thinly applied gels or patches is not known, and according to the results of the present inventors, it was not a problem that can be easily solved with generally known peroxide stabilizers.

The inventors of the present invention, while screening the peroxide stabilizer usable in the patch, in consideration of the basic physical properties of the patch to find a stabilizer that can be used within the scope of use of the present invention, and thus the stability of the peroxide in the patch over time It can be improved considerably. That is, another feature of the present invention is the use of a peroxide, a tooth whitening agent, with a peroxide stabilizer.

In the tooth whitening patch according to the present invention, stabilizers having good compatibility with peroxides include alkylaryl sulfonates, alkyl sulfonate salts, alkyl carboxylate salts, alkyl diphenyloxide disulfonates, and span 20 (Span 20, sorbitan monolaurate). Span 40, sorbitan monopalmitate, Span 60, sorbitan monostearate, Span 80, sorbitan monooleate, Span 85, sorbitan trioleate, Tween, POE sorbitan fatty acid ester) or mixtures thereof.

The peroxide and its stabilizer in the patch of the present invention will be described in more detail as follows. In the present invention, peroxide is used as the main tooth whitening agent in the patch, and when the patch is made only with these whitening agents, the peroxide content in the patch decreases over time even when stored at 40 ° C, so that the in vitro whitening effect is also lower than the first. there was. In the case of gel form, the loss of peroxide was very small without extra stabilizer even if the polymer was used as a film-forming agent in the formulation containing the same peroxide, and the formulation lacking peroxide stability was also known as a common peroxide stabilizer. For example, the desired level of stability could be obtained by adding a small amount of EDTA or sodium citrate. However, in the case of the sheet-type patch obtained by evaporating the solvent of the gel as in the present invention, when the stabilizing agent was not added even when the same prescription was used, the peroxide stability of the peroxide was lower than that of the solution state. When the chelating agent was added as in the solution, the stability of the peroxide in the patch was lower than before the addition. Moreover, even when Dequest phosphonates known to be excellent in peroxide stabilizing effects were added to the patch, peroxide stabilizing effects could not be obtained.

The reason why the same composition is different in the peroxide over time stability according to the gel, liquid, or sheet phase can be considered for various reasons. According to US Pat. No. 4,320,102, a very small amount of peroxide is catalyzed by a metal reaction. It is said that even the only metal is very sensitive to decomposition. In other words, hydrogen peroxide is decomposed even if only 0.1 mg of iron, 0.2 mg of copper, 0.1 mg of magnesium, and 0.02 mg of chromium per liter. Based on these data, sheet-shaped patches made by evaporation of solvent in solution or gel state contain relatively high amounts of metals in a thin thickness and are more peroxide-rich due to their increased surface area and higher reactivity. It seems that the stability over time becomes insufficient.

In the present invention, materials used as peroxide stabilizers in patches are mainly surfactants or emulsifiers, which form micelles on sheets to prevent contact between raw materials and incompatible materials with poor peroxides, or poor application of glass. In the case of using the polymer, the whitening agent is uniformly dispersed throughout the patch and the adhesive layer is uniformly applied, which is considered to have a positive effect on the peroxide stabilization. In fact, the gels in the container have excellent stability over time at relatively high temperatures, while the same gel formulation has been applied to a thin strip to increase the surface area. I could confirm it.

On the other hand, the present inventors have found that some of the hydrophilic glassy polymers have excellent compatibility with the peroxide, and thus, the stability of the solvent can be sufficiently maintained by properly adjusting the ratio of the solvent without adding the peroxide stabilizer. Therefore, the patch of the present invention is not limited only to the use of a peroxide and a peroxide stabilizer together. This point is explained in more detail as follows.

Polyvinylpyrrolidone (PVP, K-15 to K-120), Polyquaternium-11, Polyquaternium-39 and Polyvinyl in hydrophilic glassy polymers Pyrrolidone-vinylacetate copolymer (PVP / VA copolymer) not only dissolves well in water and ethanol but also has excellent compatibility with peroxides, so the ratio of water and ethanol is 9: 1 to 0:10 without adding peroxide stabilizer. When adjusted to the peroxide stability in the patch is excellent. The good compatibility between peroxide and polyvinylpyrrolidone is considered to be due to stabilization of polyvinylpyrrolidone and peroxide by forming a complex by hydrogen bonding. Among them, polyvinylpyrrolidone is the most preferred hydrophilic glass polymer for use as a main polymer for drug layers containing peroxides. Although PVP can use all K-15 to K-120, PVP (K-90) was preferable in this invention. However, when producing by a casting method, PVP (K-30) is more preferable because the higher the polymer content in the gel in terms of production efficiency in the manufacturing process is more preferable. PVP preferably has a relatively high molecular weight of at least 500,000 molecular weight, more preferably at least 1,000,000 molecular weight. Most preferred is PVP with a molecular weight of about 1,270,000. In addition, it was confirmed that the polymer having a quaternary ammonium structure, such as polyquaternium, has good compatibility with the peroxide.

In addition, the use of a mixed solvent of water and ethanol as a solvent of the polymer indicates that the glass polymers compatible with these peroxides are very hydrophilic and are not uniformly applied to a release liner or another sheet. This is because such a problem can be solved when a solvent is used to obtain a uniform sheet form. Therefore, another feature of the present invention is that when using a glass polymer having a good compatibility with the peroxide, using a peroxide as a tooth whitening agent and without adding a separate peroxide stabilizer, the solvent ratio of water and ethanol in the adhesive layer composition at the time of manufacture It is possible to make a patch having excellent peroxide stability at high temperature by controlling the temperature. In this case, as with the patch containing the peroxide stabilizer, a suitable plasticizer may be added depending on the polymer in order to give sufficient flexibility to the patch. Suitable plasticizers vary depending on the type of polymer and its formulation, but may be generally used polypropylene glycol, glycerin or polyethylene glycol.

On the other hand, in the tooth whitening patch of the present invention, although a peroxide is used as a main whitening agent, condensed phosphate may be used as a whitening agent together with a peroxide to improve the whitening effect. In this case, as condensation phosphates (polyphosphates) that can be used with the peroxide, for example, sodium pyrophosphate (TSPP), sodium pyrophosphate (SAPP), sodium metaphosphate (SHMP) ), Sodium tripolyphosphate (STP), sodium potassium tripolyphosphate (SKTP), potassium pyrophosphate (TKPP), ultra phosphate acidic sodium meta-polyphosphate (Sporix), Multiphos (acidic sodium polyphosphate, Multiphos), or mixtures thereof.

In general, condensed phosphates are known to be effective as tartar control agents in toothpaste to inhibit tartar formation and to remove tartar. In addition, these are good chelating agents of metals, which can effectively contribute to the improvement of whitening effect because it can effectively remove tooth stains produced by metals such as iron, calcium, and magnesium in food or working environment. Known. Therefore, the use of these polyphosphates in combination with the peroxides in the patch of the present invention is expected to be effective in inhibiting tartar formation or removing tartar by prolonging the contact time between teeth and polyphosphates as well as improving the whitening effect. In fact, when attaching the patch containing them, it was found that the tooth surface or between the teeth was clean.

In the patch of the present invention, the thickness of the drug layer can be used from thin to thick. Of course, at the time of bed, the saliva secretion is less than when it is less, so that a relatively small amount melts, but still more than a certain thickness. In the patch of the present invention, a hydrophilic glass polymer is used as the main polymer of the drug layer, and if the thickness of the drug layer is less than 50 μm, it may be completely dissolved within 4 hours depending on the type of polymer used and its solubility, and thus may not contribute to the whitening effect. It may be. Therefore, in the patch according to the present invention, the thickness of the drug layer is preferably 50 μm or more.

In the tooth whitening patch of the present invention, the polymers that can be used for the backing layer of the matrix type patch can be broadly divided into the following two types. First, a polymer used in an edible coating used to preserve the freshness and taste by maintaining a freshness by preventing the passage of moisture by coating a thin film on fruits or vegetables. These include cellulose ethers, starch, hydroxypropylated starch, corn zein, wheat gluten, soy protein, and milk protein. (milk protein), zein-acetylated monoglycerides, zein-vegetable oils, casein-acetylated monoglycerides, whey protein , Whey protein / acetylated monoglyceride, albumin + soy protein, zein / fatty acid amylase ester, and the like. In addition, edible waxes, such as casein and beeswax, in particular, these waxes are somewhat soluble in water but are not as adhesive or weakly adherent to oral tissues such as teeth or gums. When used in combination, the object of the present invention can be achieved. For example, methyl cellulose is soluble in water but can be used when mixed with beeswax to have a moisture barrier. The polymers that can be used for this purpose are: methyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, dextrins (starch hydrolysates), alginates, carrageenan (carrageenan), gelatin (gelatin) and the like.

The second polymers that can be used for the support layer in the tooth whitening patch of the present invention are polymers that are water impermeable as well as water impermeable. These include polyvinyl acetate, ethyl cellulose, polymethyl methacrylate, methacryloyl ethyl betaine / methacrylate copolymer (Yukaformer: Mitsubishi, manufacturer, metacryloyl ethyl betain / metacylate copolymer), methacrylic acid air (Methacrylic acid copolymers; Eudragit L 100, Eudragit L 12,5, Eudragit L 100-55, Eudragit L 30D-55), aminoalkyl methacrylate copolymers; Eudragit E 100, Eudragit E 12,5 , Eudragit RL 100, Eudragit RL 30D), cellulose acetate phthalate, Shellac, or mixtures thereof. In addition, enteric coating (enteric coating) material that can not be used in the oral conditions between pH 6 to 8 can be used.

The grade of polymers used in the support layer is also important in the tooth whitening patch of the present invention. That is, it is not a formula that can be removed after use for a certain period of time, but because it is a film that does not dissolve in water that can be detached when left in the teeth and naturally swallowed when eating or drinking beverages such as food or water. It is preferably a food grade or a pharmaceutical grade that can be used as a coating of a medicine or as a component of a medicine.

In order to have sufficient flexibility, such a support layer can be used by adding various plasticizers. In addition to the aforementioned plasticizers, propylene glycol, glycerine and polyethylene glycol, more plasticizers can be used depending on the solvent used and castor oil. ), Hydrogenated castor oil may also be used.

In the tooth whitening patch, both a casting method and an extrusion method are possible in order to produce a thin film with a constant thickness, but in the patch of the present invention, a casting method is more preferable. In addition, the selection of a coater is also important in order to make the most preferable thickness of 5 μm or less. That is, when manufacturing the patch of the present invention, the gravure coater (Gravure) used for printing, rather than using a comma coater (Comma Coater), which has the advantage of precisely matching the thickness but difficult to make the thickness as thin as possible It is preferred to use a coater, which is convenient when made as thin as possible, rather than precise, to a thickness of less than 5 μm. The advantage of manufacturing with such a gravure coater is that it takes less time to produce even if it is coated several times to 1 ~ 2 ㎛. By such a configuration, the dry tooth whitening patch of the present invention is characterized in that the thickness of the drug layer is at least 10 times greater than that of the supporting layer.

In addition, when the patch of the present invention is attached to the teeth, white pigments such as titanium dioxide and talc are formed on the support layer so that the whitening may be visually white as well as whitening by chemical and physical action. It is also possible to mix hydroxyapatite, zinc oxide and the like, and when these pigments are not compatible with the whitening agent of the adhesive layer, surface-treated titanium dioxide may be used. In addition to white pigments, pearl formulations or pigments of various colors may be applied depending on individuality.

In the patch of the present invention, enzymes, particularly dextranase, glucose oxidase, and the like, which are difficult to apply over time when applied to toothpaste, may be used alone or in combination, and papain, which is effective in whitening teeth, may be added. Can be. In addition, as drugs for the treatment of oral diseases, triclosan, chlorohexidin, vitamin E or derivatives thereof, especially vitamin E acetate, oxidants or chlorophyll or derivatives thereof, which are effective for removing bad breath, and spices ) Can also be added to the patch of the present invention. In addition, although a flavor can be added to both a drug layer and a support layer, it can also be added only to a support layer according to the objective.

The dry tooth whitening patch according to the invention is attached to the surface of the tooth to be whitened. Patches are divided into water-soluble and water-insoluble parts (support layer). The water-soluble part is in direct contact with the surface of the tooth, and the support layer serves as a protective wall. Dry tooth whitening patches increase hydration and increase adhesion as they are hydrated. However, it can be fully hydrated with minimal moisture, so it doesn't matter unless you deliberately wipe and dry the tooth surface. In addition, since excessive hydrophilicity of the hydrophilic glass polymer melts rapidly and the adhesion decreases rapidly, it is not preferable to consume excessive water or drink while the tooth whitening patch is attached to the teeth.

In addition, the patch according to the present invention may be a thin film that can be eaten by the support layer, in which case it is possible to attach for a long time, even if attached to the teeth and sleep, a certain amount of whitening component is released for a certain time, sufficient contact time It has a good contact time, and it can be used not only in daily life but also during bedtime because the patch is not dangerous even if the patch is separated from the tooth during bedtime.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are only illustrative to aid the understanding of the present invention, and the scope of the present invention is not limited thereto.

Examples 1-5 and Comparative Examples 1-4

Tooth whitening patches of Examples 1 to 5 and Comparative Examples 1 to 4 were prepared with the composition as described below.

Example 1

Drug-containing adhesive layer preparation solution (drug layer final thickness 300 μm):

Polyvinyl alcohol 10%, polyvinylpyrrolidone 10%, sodium pyrophosphate 5%, alkylaryl sulfonate (SLS) 2%, glycerin 3%, water to 100%.

Support layer preparation solution (support layer final thickness 5 μm):

Ethylcellulose 8%, Eudragit 5%, Castor Oil 4%, Ethanol to 100.

Example 2

Adhesive layer preparation solution (adhesive layer final thickness 5 μm):

Hydroxypropyl Cellulose 30%, Ethanol to 100%

Drug layer preparation solution (drug layer final thickness 200 μm):

Polyvinylpyrrolidone 20%, hydrogen peroxide 5%, glycerin 10%, ethanol 30%, water to 100.

Support layer preparation solution (support layer final thickness 5 μm):

10% hydroxypropyl cellulose, 5% beeswax, 2% glycerin, ethanol to 100.

Example 3

Drug-containing adhesive layer preparation solution (drug layer final thickness 50 ㎛):

Polyquaternium-39 10%, urea peroxide 10%, ethanol 50%, water to 100.

Support layer preparation solution (support layer final thickness 5 μm):

10% zein, 5% castor oil, ethanol (95%) to 100%.

Example 4

Adhesive layer preparation solution (adhesive layer thickness 2-3 micrometers):

20% polyvinylpyrrolidone, 100% ethanol.

Drug layer preparation solution (drug layer thickness 500 μm):

Polyalkylvinyl ether-maleic acid copolymer (Gantrez S 97) 12%, sodium pyrophosphate 6%, Sorbitan Oleate 0.5%, water to 100.

Support layer preparation solution (support layer final thickness 4 μm):

10% ethyl cellulose, 6% castor oil, ethanol to 100

Example 5

Adhesive layer preparation solution (adhesive layer thickness 5 micrometers):

Polyvinyl alcohol 10%, polyvinylpyrrolidone 10%, glycerin 3%, water to 100%.

Drug layer preparation solution (drug layer thickness 210 μm):

Polyquaternium-11 20%, PC 4%, TKPP 4%, Sorbitan Monolaurate 2%, water to 100.

Support layer preparation solution (support layer final thickness 5 μm):

Eudragit 15%, Propylene Glycol 5%, Ethanol to 100

Comparative Example 1

P & G wet patch Crest Whitestrips with drug layer gel applied to the backing layer:

Drug-containing adhesive layer preparation solution (drug layer thickness 200 μm):

Carbopol 12%, hydrogen peroxide 4.5%, SAPP 0.48%, glycerin 80%, water to 100

Support layer (support layer thickness 9 μm):

Polyethylene strip

Comparative Example 2

Products used by applying gel containing carbamide peroxide directly to one size tray:

Urea peroxide 10%, Carbopol 12%, glycerin 70%, water to 100

Comparative Example 3

Dry patch having the same composition as in Example 1 but having a thickness of the drug layer of 60 µm and a thickness of the supporting layer of 60 µm.

[Comparative Example 4]

Adhesive layer preparation solution (adhesive layer thickness 400 μm):

Polyvinyl alcohol 10%, propylene glycol 3.1%, kojiic acid 0.5%, trace amount of paraoxybenzoic acid methyl, water to 100%

Support layer preparation solution (support layer final thickness 200 μm):

10% ethyl cellulose, 4% castor oil, ethanol to 100

In the above examples and comparative examples, TKPP is potassium pyrophosphate (tetrapotassium pyrophosphate), SAPP is sodium pyrophosphate acid (sodium acid pyrophosphate), TSPP is sodium pyrophosphate (tetrasodium pyrophosphate).

The drug layer and support layer were prepared according to each prescription.

First, the drug layer was coated with a comma coater (Comma Coater) on the PET release liner and dried at 80 ℃ to prepare a film of the desired final thickness.

In the case of the support layer, the mixed solution was coated on a release liner, PET (Polyethylene Terephthalate) with a gravure coater (Gravure Coater), and dried at a speed of 15 m per minute at a drying temperature of 70 ℃ to prepare a film of the desired final thickness.

Subsequently, the lamination process is as follows: the drug layer coated on the PET and the support layer coated on the PET were laminated using a laminator roller. PET behind the backing layer was collected and reused.

Experimental Example 1: Evaluation of Usability

Examples 1 and 2 are dry and whitening patches, characterized in that the thickness of the support layer is 5 ㎛ or less, Comparative Example 1 was used in the Crest Whitestrip of P & G currently sold in the United States, Comparative Example 2 is Rembrandt's One Size Tray products to be. Comparative Example 3 is the same formulation as Comparative Example 1, but the drug layer and the support layer was prepared differently, Comparative Example 4 is a patch according to Example 2 of Lion's patent (Japanese Patent Laid-Open No. 10-017448).

Each patch was worn once a day and three times for four hours, after which gum irritation and wearing comfort were evaluated. The adhesion sustainability was also evaluated, and it was evaluated by how well the adhesive force was maintained even after applying it for 4 hours or more (in the case of the tray, it was evaluated by what time it was possible to bite).

Each rating is on a 5-point scale, very satisfied 5 points (no irritation, very strong tooth adhesion, very good adhesion lasting), slightly satisfied 4 points (almost no stimulation, slightly stronger tooth adhesion, slightly better adhesion lasting), moderate 3 points (sometimes irritation, moderate tooth adhesion, moderate adhesion lasting), slightly unsatisfactory 2 points (irritation at initial use, slightly weak tooth adhesion, slightly less sustained adhesion), very unsatisfactory 1 point (continuous irritation during use, very weak tooth adhesion) , Very poor adhesion sustainability). Ten individuals were evaluated for each case. Table 1 shows the results of the usability and safety evaluation.

Gum irritation Wear comfort Tooth adhesion Adhesion lasting Example 1 4 4 5 5 Example 2 4 4 5 5 Comparative Example 1 3 3 3 2 Comparative Example 2 2 2 2 3 Comparative Example 3 4 4 5 4 Comparative Example 4 2 3 3 2

As shown in Table 1, the most difference between the Example and the comparative example is the adhesion sustained by 4 hours of adhesion. In the case of tray type, it was difficult to continuously bite because it was inconvenient when used for more than 1 hour, and it was not available for more than 2 hours. In addition, in the case of Comparative Example 1, after about an hour, it was not attached to the teeth, but played separately, and was separated from the teeth even with light stimulation.

Experimental Example 2 Evaluation of Tooth Adhesion

Tooth adhesion of the patches prepared in the above Examples and Comparative Examples was evaluated by the following method.

(1) Preparation of Hydroxyapatite (HAP) Tablet Specimen

The hydroxyapatite powder was tableted by IR press and then sintered at 1000 ° C.

(2) tooth adhesion evaluation

Miniature Tensile tester was used to measure the adhesion of the patch to hydroxyapatite, an artificial tooth. Adhesion in the dry state was measured for the adhesion of the sintered hydroxyapatite specimen in a completely dry state, the adhesive force in the wet state was measured by removing the water on the surface after the water was sufficiently wetted in advance. The reason for this condition is that the mouth is actually moist but the surface of the tooth is not so wet that it appears to be moist. Adhesion of the patch to the teeth was repeatedly measured several times at regular time intervals after pressing for a predetermined time with a constant force and then removing the patch. Table 2 below shows the tooth adhesion (gmf) of these patches.

Dry adhesion Wet adhesion Example 3 0.5 210.5 Example 4 25.8 137.0 Example 5 28.5 150.4 Comparative Example 1 38.0 39.5

As shown in Table 2, in the case of dry patches Examples 3 to 5, the difference in adhesion between the dry state and the wet state is increased by 2 to 400 times, while the wet, in particular gel, is applied to the strip. In Comparative Example 1, it can be seen that there is almost no difference in the dry state and the wet state adhesion.

As described above, the present invention is a dry patch using a hydrophilic glassy polymer (glassy polymer) in the layer except for the support layer, the adhesive force is generated while hydrating upon contact with the teeth and the release of the whitening agent is more safe and hands when using It is convenient to use because it doesn't get buried in contact with other parts of the body, and it has excellent adhesion, so it doesn't detach during wearing and is completely adhered to the surface of teeth, so it shows excellent whitening effect.

In addition, the tooth whitening patch of the present invention is easy to use dry because it is excellent in the adhesion and whitening effect on the teeth and does not need to be removed after attachment, the thickness of the support layer is very thin, but preferably composed of edible ingredients for a long time Not only is it comfortable and safe to attach, it is also productive because it minimizes the cost and time required to produce the support layer.

1 is a cross-sectional view showing one embodiment of a tooth whitening patch according to the present invention.

Claims (15)

In a matrix type tooth enamel patch having a drug layer and a support layer, the drug layer includes a peroxide and a hydrophilic glassy polymer as a tooth whitening agent, so that the glass polymer is hydrated upon contact with the tooth. Dry adhesive tooth whitening patch, characterized in that the strong adhesive force is generated and the release of the whitening agent is started, the thickness of the drug layer is more than 10 times the thickness of the support layer. The tooth whitening patch of claim 1, wherein the support layer has a thickness of 5 m or less. The tooth whitening patch of claim 1, wherein the support layer is water impermeable. The tooth whitening patch of claim 1, wherein the support layer is of an edible component or grade. The method of claim 1 wherein the support layer is cellulose ethers, starch, hydroxypropylated starch, corn zein, wheat gluten, soy protein , Milk protein, zein-acetylated monoglyceride, zein-vegetable oils, casein-acetylated monoglyceride, whey protein ( whey protein, whey protein / acetylated monoglyceride, albumin and soy protein, zein / fatty acid amylase ester, casein, A tooth whitening patch characterized by beeswax, or a mixture thereof. 6. The tooth whitening patch of claim 1 or 5, wherein the backing layer is a mixture of wax and a polymer that is partially soluble in water but not adhesive or weak in tissues in the oral cavity. The method of claim 6 wherein the polymer is methyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, dextrins (starch hydrolysates), alginates, carrageenan Tooth whitening patch, characterized in that the gelatin (gelatin), or a mixture thereof. The tooth whitening patch of claim 1, wherein the support layer is both water impermeable and water insoluble. 9. The tooth whitening patch of claim 8, wherein the support layer is of an edible component or grade. The method of claim 1, wherein the support layer is polyvinyl acetate, ethyl cellulose, polymethyl methacrylate, methacryloyl ethyl betaine / methacrylate copolymer, methacrylic acid copolymer (methacrylic) A tooth whitening patch comprising an acid copolymer, an aminoalkyl methacrylate copolymer, cellulose acetate phthalate, shellac, or a mixture thereof. The method of claim 1, wherein the glass polymer is a polyalkylvinylether-maleic acid copolymer (PVM / MA copolymer), polyvinyl alcohol, polyacrylic acid, poloxamer 407, polyvinylpyrrolidone-vinylacetate copolymer (PVP / VA copolymer), polyvinylpyrrolidone (PVP), Polyquaternium-11, Polyquaternium-39, Carbomer, hydroxypropylmethyl cellulose, A tooth whitening patch, characterized in that it is hydroxyethyl cellulose, hydroxypropyl cellulose, gelatin, sodium alginate, or mixtures thereof. The tooth whitening patch of claim 1, further comprising a peroxide stabilizer together with the peroxide. The method of claim 12, wherein the peroxide stabilizer is alkylaryl sulfonate, alkyl sulfonate salt, alkyl carboxylate salt, alkyl diphenyloxide disulfonate, Span 20 (sorbitan monolaurate), Span 40 (Span 40, sorbitan monopalmitate), Span 60, sorbitan monostearate, Span 80, sorbitan monooleate, Span 85, sorbitan trioleate, Tween, POE sorbitan fatty acid ester, or mixtures thereof Tooth whitening patch, characterized in that. The tooth whitening patch of claim 1, further comprising a condensed phosphate. 15. The method of claim 14, wherein the condensed phosphate is sodium pyrophosphate (TSPP), sodium pyrophosphate (SAPP), sodium hexametaphosphate (SHMP), sodium tripolyphosphate (STP). Sodium potassium tripolyphosphate (SKTP), potassium pyrophosphate (TKPP), acidic sodium meta-polyphosphate (Sporix), multi-phosphate (acidic sodium polyphosphate, Multiphos), or Tooth whitening patch, characterized in that a mixture thereof.