WO2007066837A1 - Delivery system for tooth whitening component using in situ gelling - Google Patents

Abstract

Disclosed herein is a liquid delivery system for a teeth whitening ingredient. The liquid delivery system is water-soluble before being applied to teeth but forms a water-insoluble film on the surface of teeth in the oral cavity through in situ gelling. Since the liquid delivery system is water-insoluble after being applied and has superior adhesion maintenance to teeth and the gum, it is suitable in the case where sufficient contact time is required to attain desired whitening effects within a short period of time of use.

Description

DELIVERY SYSTEM FOR TOOTH WHITENING

COMPONENT USING IN SITU GELLING

Technical Field

The present invention relates to a delivery system for tooth whitening component which is water-soluble before being applied to teeth but forms a water- insoluble film on the surface of teeth in oral cavity through in situ gelling. The delivery system becomes water-insoluble after being applied to teeth to have superior adhesion maintenance to teeth and gum, which is thus suitable for such case that sufficient contact time is required to attain desired whitening effects within a short period of time.

Background Art

As people's interest in teeth whitening increases, a number of tray products providing teeth whitening effects within a short period of time have become commercially available. A dentist-prescribed at-home bleaching product using a custom tray so as to suit to a wearer is intended for overnight use for two weeks. However, since the wearer must keep their mouth closed while sleeping for two weeks despite the wearer's busy daily life, the product is very inconvenient to use. For this reason, dentists say that people prefer in-office bleaching products capable of providing whitening effects in only one dental surgery. In order to shorten the two-week period to one dental surgery, hydrogen peroxide at a concentration as high as 30-35% is used. In this case, an element, such as a rubber dam, must be used so as to prevent contact of the product with body parts other than teeth. As another technique, it is known that hydrogen peroxide at a low concentration of 16% can be combined with the use of laser, heat activator or photo activator so as to exert synergistic effects. The in- office bleaching product has disadvantages of severe irritation and earlier retention due to the use of high-concentration hydrogen peroxide. In addition, although there has been considerable interest in in-office bleaching products and at-home bleaching products, these products are disadvantageous in that they are expensive and wearers need to regularly visit a dentist.

Accordingly, there is a demand for over-the-counter (OTC) products for teeth whitening which can exhibit whitening effects comparable to dental surgery at low cost without the aid of a dentist. A number of teeth whitening products using trays for OTC products are now available at low cost in supermarkets and drugstores, but are known to have many problems. For example, since the OTC products use one-sized and single-shaped trays, they do not fit various sizes and shapes of user's teeth, which causes irritation to the teeth due to poor fitting trays and gels excessively applied onto the trays. In addition, since the leakage of gel may take place during use, there are problems in terms of convenience and safety. Further, since most of the OTC products are highly noticeable, it is difficult to use them on a daily basis. Furthermore, it is difficult to wear the OTC products for a long time.

In order to solve the above problems of the conventional teeth whitening products using trays, P&G filed a patent application relating to a strip for teeth whitening, which have been manufactured on a commercial scale. Since the strip for teeth whitening is manufactured by uniformly and thinly coating a teeth whitening ingredient onto a thin and flexible polyethylene strip without the use of a tray, problems of conventional tray products can be solved. Since the strip for teeth whitening is a wet type, the adhesive strength of the strip to the teeth is not so strong. Accordingly, the strip can be easily attached and peeled off, but has a drawback in that when coughing and laughing out loud, it moves and is therefore not attached at a desired position for a desired period of time and can be easily detached from teeth. Since the strip for teeth whitening has poor adhesion to teeth, a wearer feels an unnatural sensation. In addition, since the strip is not closely fixed to teeth, a wearer feels that the strip is loose and cannot continuously wear the strip for 30 minutes or more. Furthermore, since the strip has poor adhesion to teeth when compared to other attachment-type products, sites between highly indented teeth and a highly irregular row of teeth, including snaggleteeth, cannot be sufficiently whitened.

USP 5,425,953 (1992) to Sintov et al. discloses a composition containing a water-soluble, low-viscosity cellulose polymer as a film- forming agent and a bleaching agent for the purpose of teeth whitening and other dental uses. The composition is a liquid formulation to be spread on teeth. Since the composition has a low viscosity, it can be spread on sites between teeth or irregular teeth so that the drawbacks of tray products and strip products can be solved. However, since the water-soluble cellulose polymer may be diluted or dissolved within 5 minutes, the composition has a serious drawback in that a sufficient contact time between the whitening ingredient and teeth cannot be guaranteed.

USP 6,569,408, USP 6,589,512 and USP 6,692,727, all of which were issued to Yue et al., disclose methods for the delivery of effective ingredients, including teeth whitening ingredients, to the oral cavity using organosiloxanes. Since the organosiloxanes are highly hydrophobic, they are not readily dissolved in and removed from the moist oral cavity. However, the hydrophobicity of organosiloxanes impedes diffusion of hydrophilic drugs, particularly a strong oxidant as a teeth whitening agent, which makes it difficult to attain desired effects within a short period of time. Further, the use of a large amount of the organosiloxanes may give a messy feeling after being applied to teeth. To overcome these problems, US Patent Publication No. 2004/0037789 (Moneuze et al.) discloses the addition of a water-soluble gel thickener essentially containing 10% or less of an organosiloxane, which gives a messy feeling after being applied to teeth.

US Patent Publication No. 2003/0219390 (Santarpia et al.) discloses a tooth whitening liquid composition comprising a carbomer with a poly( ethylene oxide). The liquid composition contains 20-30% of ethanol as a solvent. When the liquid is applied to dry teeth, the solvent is vaporized to allow the poly(ethylene oxide) as a film-forming agent to form a film. At this time, the film is sticky due to the carbomer, and thus it can remain on the teeth for a desired time. However, the desired film may not be adequately formed on the teeth surface when the drying time is insufficient due to various factors, e.g., the spreading thickness of the ethanol, the dry state of the teeth and the humidity of the oral cavity. Further, since the poly(ethylene oxide) film is water-soluble, the film may be diluted or dissolved in saliva.

Another problem associated with the use of the tray and strip products is that the viscosity of polymers used in the products is lowered at elevated temperatures and thus a gel may run down from the products during use in the oral cavity at a relatively high temperature.

To solve this problem, USP 6,312,666 to Oxman et al. mentions a delivery system for teeth whitening using a formulation whose temperature is increased in the oral cavity. Based on this characteristic of the delivery system,

Oxman et al. suggested a product capable of solving the problem associated with the use of conventional trays and strips, i.e. difficult application to sites between teeth and to an irregular row of teeth, in USP 6,620,405. The patent describes a system which can be applied to teeth using a brush or by spraying because the system is a low-viscosity liquid during storage at room temperature and before being spread, but is converted to a gel having no mobility because the system becomes highly viscous due to the temperature of the oral cavity after being applied to teeth.

Changes in viscosity according to the application in the oral cavity are induced by the thermosensitivity of poloxamer. Transition takes place from a sol below the gelling temperature of the poloxamer to a gel above the gelling temperature of the poloxamer. Poloxamer is a good system in currently available suppositories but may cause problems in some systems, e.g., the oral cavity where a large amount of saliva is continuously secreted. Poloxamer has a high gelling temperature at a low concentration. Accordingly, when a product is diluted in saliva in the state wherein the product becomes a gel after being applied to teeth, the gelling temperature of the poloxamer is increased and thus converts the gel to a sol, after which the sol is easily removed and thus desired results are not readily obtained.

Disclosure of Invention

Technical Problem

Therefore, the present invention has been made in view of the above problems, and it is an object of the present invention to provide a delivery system for a teeth whitening ingredient that is a low-viscosity liquid when being applied to teeth and is readily applicable to gaps between teeth and to irregular teeth to form a water-insoluble film in oral cavity, thereby exhibiting superior adhesion maintenance to the teeth.

Technical Solution

In accordance with one aspect of the present invention for achieving the above object, there is provided a liquid delivery system for a teeth whitening ingredient which comprises a first agent containing a water-soluble calcium ion source, and a second agent containing a water-soluble alginate wherein at least one of the first agent and the second agent contains a material for improving adhesion to teeth and a teeth whitening ingredient.

In accordance with another aspect of the present invention, there is provided a liquid delivery system for a teeth whitening ingredient which comprises a first agent containing a water-insoluble calcium ion source, and a second agent containing an acid capable of causing the water-insoluble calcium ion source of the first agent to generate water-soluble calcium ions wherein at least one of the first agent and the second agent contains a water-soluble alginate, a material for improving adhesion to teeth and a teeth whitening ingredient.

In accordance with another aspect of the present invention, there is provided a liquid delivery system for a teeth whitening ingredient which comprises a first agent containing a water-soluble calcium ion source, a peroxide as the teeth whitening ingredient and silica, and a second agent containing a water-soluble alginate wherein at least one of the first agent and the second agent contains a material for improving adhesion to teeth.

In accordance with yet another aspect of the present invention, there is provided a liquid delivery system for a teeth whitening ingredient which comprises a first agent containing a water-insoluble calcium ion source, a peroxide as the teeth whitening ingredient and silica, and a second agent containing an acid capable of causing the water-insoluble calcium ion source of the first agent to generate water-soluble calcium ions and a water-soluble alginate wherein at least one of the first agent and the second agent contains a material for improving adhesion to teeth.

The delivery system for a teeth whitening ingredient according to the present invention is a system for delivering effective ingredients to the oral cavity to form a water-insoluble gel or film through in situ gelling when being applied to teeth in the oral cavity. The delivery system of the present invention uses in situ gelling of the alginate to form a water-insoluble film on the surface of teeth within a short time when the first agent joins the second agent. That is, the water- soluble polymer alginate joins calcium ions to form a water-insoluble gel or film. Accordingly, the delivery system of the present invention is advantageously not affected by various conditions of the oral cavity, e.g., pH, temperature, water content, etc., and is safe because no organic solvent is used, hi addition, since the hydrophilic composition is highly spreadable when being applied to teeth, which are also hydrophilic, it offers convenience while being used and can avoid a messy feeling caused when a hydrophobic composition, such as silicone, is used. Furthermore, since the delivery system of the present invention contains a polymer having superior adhesion maintenance to teeth and mucous membranes of the gum in the oral cavity, it can remain at desired sites for a desired time due to its sufficient adhesion maintenance to the sites after a water-insoluble alginate film or gel is formed on the desired sites. Also, since the delivery system of the present invention forms a very thin film, no unnatural sensation is felt. Since the ingredients are edible, there is no need for the removal of the ingredients after use.

Based on these characteristics and advantages, since the delivery system of the present invention is simply applied to teeth once or twice daily using a suitable instrument, such as a brush, it offers convenience while being used.

Best Mode

The delivery system for a teeth whitening ingredient according to present invention will now be described in more detail.

The delivery system of the present invention overcomes the problems of conventional attachment-type products and tray products, e.g., need for removal after use, and difficult whitening of sites between teeth and non-uniform application to snaggleteeth due to poor flexibility or elasticity. In addition, the delivery system of the present invention solves the problems associated with the use of conventional spreadable whitening agents, e.g., immediate dissolution of hydrophilic films formed on teeth due to the action of saliva, a messy feeling of lipophilic films, and difficult diffusion of whitening ingredients. These advantages of the delivery system according to the present invention can be achieved by the formation of a water-insoluble film on the surface of teeth after being applied to teeth. Advantageously, since the delivery system of the present invention is hydrophilic before being applied to teeth, it is highly spreadable on the teeth, hi addition, since the delivery system of the present invention forms a water-insoluble film and has superior adhesion maintenance to teeth after being applied to the teeth, it can remain on the teeth in the oral cavity for a desired time, thus ensuring a sufficient contact time, which is an essential factor to attain whitening effects within a short period of time.

Most advantageously, the delivery system of the present invention is a system suitable for delivering a teeth whitening ingredient to the moist oral cavity. In recent years, in situ gelling systems using environmental sensitive polymers have been introduced as systems for controlling the delivery of effective ingredients. Most of such in situ gelling systems are effective in internal environments of the body whose temperature is always maintained at 37°C and at sites where humidity is maintained to some degree. However, the application of in situ gelling systems is limited in some places, such as the oral cavity, where sudden temperature changes are frequently caused due to cold beverages and hot foods, and saliva is always secreted, particularly, saliva is excessively secreted by foreign materials entering the oral cavity. In addition, since some compositions applied to teeth in the oral cavity may be eaten, ingredients that can be used in the compositions are very limited. Thus, the polymer used in the present invention is a polysaccharide having a natural carboxylate group as a pendant. The polymer is widely used for various purposes in the fields of foods, and is a safe ingredient commonly used in the fields of pharmaceuticals. In addition, since the delivery system of the present invention uses water as a solvent, it is advantageous in terms of sensitivity. Hydrogel formulations maintain their shapes by water absorption. Since hydrogel formulations are water insoluble but hydrophilic, they are advantageous over other polymer systems. However, since most hydrogel formulations have covalently crosslinked networks, which generally have a chemical toxicity, they are not suitable to use in the oral cavity. In contrast, the delivery system of the present invention uses a non-covalent crosslinking with a physical gel. Since the delivery system of the present invention uses divalent or trivalent cations, e.g., calcium ions, as crosslinkers, it is harmless to humans.

The term "water-insoluble film" as used herein refers to a thin film insoluble in water, and includes film-like gels having a high viscosity and no flowability. Meanwhile, the term "liquid" as used herein refers to a state that has a relatively low viscosity and is flowable.

The phrase "in situ" referred to herein has a dictionary meaning originating from the Latin language and the Greek language and refers to "in its proper position" in English. The phrase "in situ gelling" refers to gelling occurring at a desired site (by inducing a reaction at a desired site).

Gels prepared through crosslinking of polysaccharides having a carboxylate group as a pendant have been used in the dental impression material and food preparation technologies. Of these, water-insoluble alginate gels are mainly used. A water-insoluble alginate gel is commonly prepared when a water-soluble alginate is converted to an insoluble alginate by a reaction with divalent or trivalent cations in an aqueous solution.

Calcium ions are cations that are most mainly used to produce a water- insoluble alginate gel. Calcium chloride is a compound used to generate calcium ions. In addition to calcium chloride, any compound that easily generates calcium ions in water can be used in the present invention. Easy generation of calcium ions includes simple dissolution in water and generation of calcium ions via a reaction with an acid.

Since a reaction to prepare the water-insoluble alginate gel occurs through a crosslinking between calcium ions and an alginate, the reaction rate is most significantly affected by the concentration of the calcium ions. When water- soluble calcium ions are used, the control over the concentration of calcium ions in a solution can be achieved by controlling the concentration of calcium ions in the composition. When water-soluble calcium ions are generated by joining an acid or controlling the pH, the control over the concentration of calcium ions in a solution can be achieved by controlling the concentration of water-insoluble calcium ions or the concentration of the acid. In addition to the direct control over the concentration of calcium ions, a gel retarder can be used. The reason for the use of the gel retarder is that the solubility of calcium poorly soluble or insoluble in water can be increased by raising the pH of the solution.

Gelation of the alginate may occur through three mechanisms, i.e. diffusion setting, internal setting, and setting by cooling. The delivery system of the present invention is not particularly limited to one of the three mechanisms. Considering that the delivery system of the present invention is applied to teeth in the oral cavity, diffusion setting and internal setting are preferred over setting by cooling. In order to autonomously control the reaction rate so as to cause in situ gelling after being uniformly applied to desired sites, internal setting is preferred over diffusion setting.

Diffusion setting is the simplest mechanism among the three mechanisms, and is mainly used in encapsulation using an alginate. According to diffusion setting, calcium ions are diffused into an alginate solution to prepare a gel. Since the diffusion rate is low, diffusion setting is suitable only for the production of thin strips or for the surface coating. According to diffusion setting, the diffusion rate is increased with increasing concentration of calcium ions, which satisfies the object of the present invention to form a thin film on teeth and the gum in the oral cavity to a significant extent. Since the reaction rate is too high during diffusion setting, however, gelation may occur as soon as the first agent joins the second agent before being applied to desired sites of teeth. Although the reaction rate can be controlled by controlling the concentration of calcium ions or the water-soluble alginate or by the addition of a gel retarder, diffusion setting is disadvantageous over internal setting in that the reaction speed cannot be easily controlled. For gelling by diffusion setting, calcium chloride is generally used as the calcium ion source. Since calcium chloride produces an unpleasant smell, it may be unsuitable when used at a high concentration, hi this case, the use of calcium lactate is preferably considered.

Internal setting is also referred to as "bulk setting". Internal setting normally takes place at room temperature, and has an advantage in that generation of calcium ions is controlled in a system. Calcium ion sources that are insoluble in water under neutral or alkaline conditions and are capable of generating calcium ions under acidic conditions are suitable in internal setting. Examples of suitable calcium ion sources include calcium sulfate, hydrated calcium sulfate, dicalcium phosphate, and calcium carbonate. As mentioned above, any calcium source can be used in internal setting that is insoluble in water under alkaline conditions and is capable of generating free calcium ions under acidic conditions or when combined with an acid. The advantage of internal setting is that calcium ions are generated at a high rate. When it is intended to retard the rate, methods that can be employed in diffusion setting can be applied. Particularly, the rate can be retarded by controlling the kind and concentration of the acid used.

Setting by cooling is a mechanism wherein a gelling ingredient, an alginate, a calcium salt, sequestrant and the like are dissolved in hot water, and the solution is cooled, thereby achieving setting. However, since most teeth whitening ingredients are unstable against heat, the dissolution may be problematic. In addition, since the temperature of the oral cavity is higher than room temperature, setting by cooling may cause an inconvenience in use without an external aid.

Gelling of water-insoluble alginates through the above gelling mechanisms is mentioned in USP 3,455,701, UK Patent 1,579,324, USP 2,756,874, USP 4,381,947, USP 4,401,456, and the catalog "Alginates in Foods" (ISP). SE 424,956 describes the use of water-insoluble alginate gel for wound dressing. The water-insoluble alginate gel is prepared by joining a water-soluble alginate with calcium ions to form a crosslinked water-insoluble paste on a wound site. In this connection with wound dressing, DE 3601132 describes the use of an alginate gel to protect mucous membranes and to deliver effective ingredients. This patent mentions that diffusion setting is employed as an in situ gelling mechanism and an increase in the adhesion of the alginate gel to mucous membranes is achieved by sequentially applying a calcium ion solution and an alginate solution. However, this increase in adhesion may be effective in mucous membranes of sites where movement is slightly restricted, but it is difficult to ensure sufficient adhesion to the surface of the oral cavity, particularly, teeth.

Accordingly, the largest problem that must be solved when an alginate is used to form a water-insoluble alginate gel in the oral cavity and a teeth whitening ingredient is delivered to teeth, is to ensure sufficient adhesion maintenance. A water-insoluble film is formed when in situ gelling occurs in an alginate, but the alginate film exhibits no stickiness, i.e. no adhesion and adhesion maintenance to teeth, in view of the inherent characteristics of the alginate film.

The present inventors have conducted intensive studies to solve the above problems. As a result, the inventors have developed a delivery system for a teeth whitening ingredient that is harmless to humans, has a gelation time sufficient to offer convenience while being used, and can be readily attached to teeth. To this end, a polymer is preferred that has superior adhesion and adhesion maintenance to teeth and is compatible with an alginate without impeding the mechanism of in situ gelling. More preferably, the gelling time is not extended by the addition of the polymer. Taking into consideration the sensitivity and toxicity, a highly water-soluble polymer is preferred because water is preferred as a main solvent in the delivery system of the present invention. Most preferred is a polymer that has increased adhesion and/or adhesion maintenance to teeth and mucous membranes but has no adhesion to the parts opposite to the teeth and mucous membranes.

Examples of suitable polymers that satisfy the above requirements include polyvinyl pyrrolidone (PVP), shellac, rosin, polyacrylic acid (PAA), carbopol, carbophil, polysaccharides, polymethyl vinyl ether/maleic acid copolymers (Gantrez), chitosan, hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose (HEC), methyl cellulose (MC), polyox, polyethylene glycol (PEG), poly(N-isopropylacrylamide), poly(N- isopropylacrylamide-co-acrylic acid), poloxamer, pulluran, polyvinyl alcohol (PVA), guar gum, carrageenan, polyacrylate, polyacrylamide, polymethacrylate, polyethacrylate, poly(acrylamide), poly(methacrylate), poly(hydroxyalkylmethacrylate), poly(maleic anhydride), poly(maleate), poly(amide), poly(ethylene amine), and poly(propylene glycol). These polymers may be used alone or in any combination. Polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA) and hydroxypropylmethyl cellulose (HPMC) are preferred, and HPMC is most preferred. These polymers may be dissolved in water before use, and may be crosslinked to prepare hydrogels. The hydrogels may be used alone or in combination with the polymers. Hydrogels prepared by crosslinking polymers having superior adhesion to teeth absorb water, further enhancing the adhesion to teeth, and are water-insoluble so that their shape is maintained. Accordingly, the hydrogels have an advantage of high retention in the moist oral cavity. The hydrogels can be applied in the form of micronized powders.

Particularly, in the case where a thermally sensitive polymer, such as poloxamer, poly(N-isopropylacrylamide) or poly(N-isopropylacrylamide-co- acrylic acid), is used in combination with the alginate or other polymers, the adhesion is increased and the rigidity is varied depending on changes in temperature. Accordingly, a delivery system having superior mechanical strength can be attained when the gelling temperature of these polymers is equal to the temperature of the oral cavity, which is higher than room temperature.

In the case where diffusion setting is employed as the mechanism of in situ gelling in the present invention, the first agent is an aqueous solution essentially containing a water-soluble calcium ion source and the second agent is an aqueous solution essentially containing a water-soluble alginate. At this time, a polymer for improving the adhesion to teeth and a teeth whitening ingredient are included in one or both of the first and second agents. The delivery system of the present invention can be applied to teeth in the form of a spray, mouthwash, paste, ointment, gel, or liquid. The first and second agents can be separately packaged into different formulations. Alternatively, the first and second agents can be mixed in a two-barrel container having one orifice before use, and then the mixture can be applied to desired sites. Even when the first and second agents are separately packaged, a mixture of the first and second agents can be prepared just before use and then it can be applied to desired sites. Alternatively, the first and second agents are sequentially applied to desired sites, or vice versa.

In the case where internal setting is employed as the mechanism of in situ gelling in the present invention, the first agent essentially contains a water- insoluble calcium ion source, unlike in the first agent used in diffusion setting, and the second agent essentially contains an acid capable of reacting with the water-insoluble calcium ion source of the first agent to generate water-soluble calcium ions. At this time, a water-soluble alginate and a polymer for improving the adhesion to teeth are included as essential ingredients in one or both of the first and second agents. A teeth whitening ingredient may be included as essential ingredients in one or both of the first and second agents. As mentioned in the diffusion setting, the delivery system of the present invention can be applied to teeth in the form of a spray, mouthwash, paste, ointment, gel, or liquid. The first and second agents can be separately packaged into different formulations. Alternatively, the first and second agents can be mixed in a two-barrel container having one orifice before use, and then the mixture can be applied to desired sites. Even when the first and second agents are separately packaged, a mixture of the first and second agents can be prepared just before use and then it can be applied to desired sites. Alternatively, the first and second agents are sequentially applied to desired sites, or vice versa.

As the alginate that is essentially included in both diffusion setting and internal setting, irrespective of other mechanisms, any grade product that is used in the oral cavity can be used in the present invention. A grade having a high content of L-guluronic acid (G-block), which is a moiety capable of bonding with calcium ions to cause gelling, is more preferred in terms of superior in situ gelling and short gelling time within a desired range. The reason for this is that two G- blocks of the alginate are arranged in parallel during formation of the water- insoluble alginate to form diamond-like holes whose area cooperatively binds with calcium ions. Accordingly, in the present invention using gelling between an alginate and calcium ions, the use of an alginate having a high G-block content is preferred over the use of an alginate having a high M-block content in the alginate consisting of G-block and M-block. The use of an alginate having a high G-block content facilitates desired gelling even at a lower polymer concentration and a low calcium concentration, promotes the formation of a gel, and improves the physical properties. For example, sodium alginate Manugel DMB (ISP), which is used in foods and has a high G-block content, has the above-mentioned advantages.

The selection of the alginate may be varied depending on the kind of desired formulations. This is because formulations have different characteristics, particularly viscosity. A desired viscosity can be attained by partially controlling the concentration of the alginate, and by selecting an alginate having a desired viscosity grade (low, intermediate, high viscosity, etc.). The concentration of the alginate may be slightly different according to the viscosity grades of the alginate. The concentration of the alginate is preferably 15% or less, more preferably 10% or less, and most preferably 5% or less.

A superporous hydrogel or an effervescent, which is used for wound dressing, may be added to the delivery system of the present invention in order to increase the diffusion rate of the effective ingredients. This addition cannot be applied to diffusion setting, but can be applied to internal setting. That is, in the case where internal setting is employed as an in situ gelling mechanism, when an acid contained essentially in one chamber joins another acid in the other chamber, an effervescent can be added to form bubbles (or foam). The bubbles thus formed broaden the surface area contacting with effective ingredients and make the surface porous, thus increasing the diffusion rate of the effective ingredients. The effervescent may be alkali metal carbonate or alkali metal bicarbonate. Examples of suitable effervescents include, but are not limited to, sodium carbonate, sodium bicarbonate, calcium carbonate, potassium carbonate, and mixtures thereof. The effervescent is not particularly restricted so long as it can be used in pharmaceuticals and foods acceptable in the oral cavity.

Examples of the water-soluble calcium ion source as an essential ingredient of the first agent in diffusion setting include calcium chloride, calcium lactate, calcium citrate, calcium aspartate, calcium saccharate, calcium oxovalerate, calcium gluconate, calcium lactobionate, and calcium lactogluconate. The water-soluble calcium ion source is not specially restricted so long as it can be used in the oral cavity and is water-soluble. Preferred are calcium chloride, calcium lactate, calcium lactogluconate, and mixtures thereof.

Examples of the water-insoluble calcium ion source as an essential ingredient of the first agent in internal setting include, but are not limited to, calcium carbonate, calcium phosphate dibasic (CaHPO₄), barium carbonate, zinc carbonate, and mixtures thereof. The water-insoluble calcium ion source is not particularly restricted so long as it is used in pharmaceuticals and foods acceptable in the oral cavity and is capable of joining an acid to generate water-soluble calcium ions.

Since the acid, which is an essential ingredient in internal setting, is used in the oral cavity and a portion of the acid may be eaten, it must be permitted in the fields of pharmaceuticals and foods. Suitable acids are acetic acid, citric acid, tartaric acid, succinic acid, formic acid, glycolic acid, malonic acid, dichloroacetic acid, oxalic acid, lactic acid, malic acid, gluconic acid, adipic acid, fumaric acid, alginic acid, maleic acid, and mixtures thereof.

The teeth whitening ingredient used in the delivery system of the present invention is not particularly limited so long as it can be applied to teeth in the oral cavity to exert whitening effects. A strong oxidant is effective as the teeth whitening ingredient. The teeth whitening ingredient is not particularly restricted so long as it exerts teeth whitening effects and can be used in products acceptable in the oral cavity. Examples of suitable teeth whitening ingredients include peroxides and metal chlorites. As specific examples of peroxides, there can be mentioned hydrogen peroxide, carbamide peroxide, calcium peroxide, perborates, percarbonates, peroxyacids, and persulfates. Sodium percarbonate is most preferred among percarbonates. As specific examples of metal chlorites, there can be mentioned calcium chlorite, barium chlorite, magnesium chlorite, lithium chlorite, sodium chlorite, and potassium chlorite. These teeth whitening ingredients may be used alone or in any combination.

On the other hand, it is necessary to uniformly apply the delivery system using in situ gelling according to the present invention to teeth. The viscosity of the first and second agents has a great influence on the uniformity of application. For example, in the case where a peroxide as the teeth whitening ingredient is contained in the first agent and an alginate is contained in the second agent, the use of an additional thickener for increasing the viscosity is required in the first agent but is not required in the second agent, hi terms of effective teeth whitening, it is particularly preferred to apply the first agent containing the peroxide to teeth so that the first agent is in direct contact with the teeth. If the first agent has a low viscosity similar to water, only a portion of the first agent is gelled with the alginate of the second agent and a considerable portion of the first agent runs down. As a result, an amount of the peroxide lower than the intended level will be used for whitening. Since an organic polymeric material is commonly used as a thickener, it tends to be structurally modified by the peroxide during storage at high temperature. Accordingly, when the polymer used as a thickener has low compatibility with the peroxide, some of the peroxide and viscosity is lost. Even when the polymer is highly compatible with the peroxide, a loss in viscosity inevitably takes place.

Particularly, the system according to one embodiment of the present invention essentially contains a considerable amount of water-soluble calcium ions for in situ gelling with the alginate. However, since calcium also has low compatibility with the peroxide, the decomposition of the peroxide is accelerated during storage at high temperature. In this case, for achieving teeth whitening effects using in situ gelling of the alginate, it is important to search for a thickener capable of increasing the viscosity of the first agent essentially containing the peroxide and the water-soluble calcium ion source and is also capable of maintaining the viscosity during storage at high temperature without causing a loss of the peroxide.

The present inventors have conducted intensive research through a series of experimental trial and error to solve the problems of deteriorated viscosity and instability that may be caused when a peroxide is used as the teeth whitening ingredient in the system of the present invention. As a result, the present inventors have found that a system using an inorganic material is more suitable than that using an organic material. In a preferred embodiment of the present invention, the delivery system essentially contains an inorganic thickener. Even if a highly reactive peroxide is used as the teeth whitening agent of the delivery system, no or little peroxide and viscosity are lost during long-term storage at high temperature. As a consequence, since all the peroxide is completely used in the in situ gelling, uniform whitening effects can be attained immediately after preparation and even after long-term storage at high temperature.

Examples of suitable inorganic thickeners include fumed silica and precipitated silica of various grades. Fumed silica is more preferred. Representative commercially available products of fumed silica are Cab-O-Sil (Cabot) and Aerosil (Degussa). A representative commercially available product of precipitated silica is Zeodent (Huber). Since fumed silica is produced by the hydrolysis of a chlorosilane in a flame of hydrogen and oxygen at a high temperature of 1,000⁰C, it advantageously has a high purity. Further, fumed silica whose surface is not treated is hydrophilic and has an advantage of easy wetting. Surface-treated fumed silica is lipophilic and water-repellent. These fumed silica products may be used alone, but is used in a mixture thereof in order to obtain desired physical properties. Examples of the hydrophilic fumed silica include LM-130, LM-150, LM-150D, M-5, M-5P, M-7D, PTG, MS-55, MS-75D, H-5, HP-50, HS-5 and EH-5, which are produced by Cab-O-Sil, and Aerosol 90, Aerosil 130, Aerosil 150, Aerosil 200, Aerosil 300 and Aerosil 380, which are produced by Degussa. Examples of the lipophilic fumed silica include, but are not limited to, TS-720 (Cab-O-Sil), and Aerosil R202, Aerosil R805, Aerosil R812, Aerosil R812S, Aerosil R972 and Aerosil R974, which are produced by Degussa.

In the preferred system of the present invention, the content of the inorganic thickener may vary depending on the grade of the silica used and the desired viscosity. For example, the hydrophilic silica, the lipophilic silica or a mixture thereof can be used in an amount of 0.5% to 30%, preferably 2.5% to 25%, and more preferably 5% to 20%.

If the fumed silica alone is used to increase the viscosity of the preferred system according to the present invention, the viscosity is maintained during storage at high temperature but a partial loss of the peroxide is observed. This phenomenon can be more clearly observed when the polymer is added to improve the adhesion and adhesion maintenance to teeth. To prevent the phenomenon, a chelating agent is added as a peroxide stabilizer or a gel retarder effective in the in situ gelling system using an alginate and calcium ions.

The chelating agent can be used, irrespective of diffusion setting and internal setting. Examples of gel retarders (or calcium sequestrants) that are used in edible formulations acceptable on teeth in the oral cavity include sodium hexametaphosphate, tetrasodium pyrophosphate, and sodium citrate.

The gel retarder chelates calcium ions in the composition to lower the concentration of the calcium ions reacting with the alginate, thereby retarding the gelling rate. Particularly, the gel retarder also acts as a peroxide stabilizer in the system using the peroxide according to the present invention. For example, in the case where a peroxide as the teeth whitening agent and the calcium ion source are included in the first agent and silica is used as a thickener, the peroxide is highly stable with time during storage at high temperature. However, depending on the grade of ingredients used and/or addition of an ingredient for increasing the adhesion to teeth, decomposition of the peroxide is more or less promoted during storage and whitening effects of the peroxide may be deteriorated in use after long-term storage. A chelating agent as the gel retarder is added to chelate metal ions having low compatibility with the peroxide, thereby solving the above problems.

In the in situ gelling system of the present invention, the peroxide is used as a main whitening agent, and a polyphosphate may be further used to improve the whitening effects along with the peroxide. Examples of preferred polyphosphates that can be used in the present invention include tetrasodium pyrophosphate (TSPP), sodium acid pyrophosphate (SAPP), sodium tripolyphosphate (STP), sodium potassium pyrophosphate, tetrapotassium pyrophosphate (TKPP), acidic sodium metaphosphate, and acidic sodium polyphosphate. These polyphosphates can be used alone or in combination with the strong oxidant. Generally, the polyphosphates are known to be effective as tartar removal agents or anticalculus agents contained in toothpastes. In addition, since the polyphosphates are good metal chelating agents and can effectively remove tooth stains formed by metals, such as iron, calcium and magnesium, contained in foods or working circumstances, it is known that the polyphosphates contribute to the improvement in whitening effects to some extent. Accordingly, since the combined use of the polyphosphate with the strong oxidant in the system of the present invention improves whitening effects and extends the contact time between teeth and the polyphosphate, it is expected to be effective in the inhibition of the formation of tooth stains and removal of tooth stains. It is preferred that the above-mentioned teeth whitening ingredients be highly compatible with not only the alginate but also the composition of the present invention.

The advantage that the delivery system of the present invention can remain for a desired time after being applied to teeth provides teeth whitening effects and may be effective in simultaneous or separate delivery of the teeth whitening ingredient and effective ingredients to the oral cavity. Examples of effective ingredients that can be simultaneously or separately applied to the oral cavity, along with the teeth whitening ingredient, include anticalculus agents, fluoride ion sources, antimicrobial agents, dentinal desensitizing agents, anesthetic agents, antifungal agents, anti-inflammatory agents, H-2 antagonists, anticaries agents, remineralization agents, vitamins, minerals, and the like.

Among these effective ingredients, specific examples of fluoride ion sources include sodium fluoride, stannous fluoride, indium fluoride, amine fluoride, and sodium monofluorophosphate. A preferred reminerlaization agent is hydroxyapatite, which is a main constituent component of teeth. Examples of reminerlaization agents include agents capable of forming in situ hydroxyapatite via a reaction. Specific examples of anticalculus agents include agents capable of chelating calcium ions, such as polyphosphates and pyrophosphates. These anticalculus agents are effective in teeth whitening. Since the ingredients for improving whitening effects are already mentioned above, the detailed explanations thereof are omitted. Specific examples of antimicrobial agents include triclosan, chlorhexidine, alexidine, hexetidine, sanguinarine, benzalkonium chloride, salicylanilide, domiphen bromide, cetylpyridinium chloride (CPC), and tetradecylpyridinium chloride (TPC). Essential oils can also be used. Specific examples of anti-inflammatory agents include aspirin, ketorolac, flurbiprofen, piroxicam, and meclofenamic acid. Specific examples of vitamins and minerals include thiamine, riboflavin, nicotinic acid, pantothenic acid, pyridoxine, biotin, folic acid, vitamin B₁₂, lipoic acid, ascorbic acid, vitamin A, vitamin D, vitamin E, and vitamin K. Coenzymes can also be included.

As the gelling time is short in the in situ gelling using a suitable alginate in the delivery system of the present invention, consumers feel comfortable. Since the delivery system of the present invention uses no volatile solvent, it is not necessary for users to open their mouth for a longer time than is needed to sufficiently dry the delivery system. Accordingly, the delivery system of the present invention is more convenient in use than conventional products. Special care must be taken to maintain the applied state until gelling. The time taken to gel is limited to 5 minutes or less, preferably 1 minute or less, and most preferably 30 seconds or less. However, the gelling time may be varied depending on the usage of the delivery system. For example, since the first and second agents must be uniformly mixed in a two-barrel container having one orifice before being applied, the delivery system must be designed taking the mixing time into consideration.

The delivery system of the present invention can be applied in various formulations in accordance with various methods. Such formulations include, for example: those having reduced viscosity, such as hairsprays; those that can be spread on desired sites by touching, such as aqueous poultices; those that can be applied using brushes, such as manicures; those that can be applied using toothbrushes, such as toothpastes, those that can be used by gargling, such as mouthwashes; and those that can be squeezed through a small hole, such as high- quality cosmetics. These formulations can be directly applied to teeth by squeezing or can be squeezed on separate instruments, such as containers and brushes, before being applied to teeth.

Further, the first and second agents may be separately used in the delivery system of the present invention, hi this case, the application of the first and second agents can be performed in various methods. Specifically, the first agent can be applied to teeth using a toothbrush, and then the second agent can be brought into contact with the teeth using a mouthwash by gargling. Of cause, both first and second agents can be applied to teeth using a brush in accordance with the same method. Various combinations are possible. The first and second agents can be mixed in a two-barrel or two-chamber container having one orifice without separately using the agents.

When the first and second agents of the system according to the present invention are separately packaged, the first agent is first applied to teeth using an appropriate instrument and then the second agent is applied thereto, or vice versa. For example, the formulation can be applied to teeth by spraying a spray, spreading a liquid having a suitable viscosity using an appropriate instrument (e.g., a brush), or spreading a paste (e.g. a toothpaste) using an appropriate instrument (e.g., a toothbrush). According to the delivery system of the present invention, the first agent combines with the second agent to form a film within a short time without being affected by various conditions of the oral cavity. Since the film thus formed is edible, it can be easily removed during daily life, e.g., eating foods, drinking beverages and brushing teeth without the need for the removal of the film.

Alternatively, the system of the present invention can be directly applied to teeth, instead of separate application of the first and second agents. To this end, the first and second agents are mixed just before use and then the mixture is applied to teeth using an appropriate instrument. For example, the first and second agents are mixed in a two-barrel container having one orifice just before use, and then the mixture discharged through the orifice of the container is applied to teeth using an appropriate instrument.

As explained earlier, according to the delivery system of the present invention, the film formed on teeth has superior adhesion maintenance to teeth. In addition, since the film is water-insoluble, it can be maintained at desired sites for a desired time although saliva is naturally secreted or excessively secreted by a foreign material suddenly entering the oral cavity. The system of the present invention more effectively whitens teeth in the absence of food or beverage until the desired time of use after being applied. The system of the present invention is still convenient while being used despite drinking a slight amount of water or beverage.

Moreover, since the delivery system of the present invention comprises no backing layer, it is safe and suitable for overnight use. Particularly, since a relatively small amount of saliva is secreted and movements are few in the oral cavity while sleeping, there is no danger that the delivery system of the present invention may be dissolved while sleeping, which ensures a sufficient contact time between the delivery system and teeth. Accordingly, the delivery system of the present invention attains satisfactory whitening effects within a short period of time. Since the delivery system of the present invention is not lipophilic, it does not give a messy feeling. Accordingly, the delivery system of the present invention gives a comfortable feeling while being used despite retention for a long time.

Mode for Invention

The present invention will now be described in more detail with reference to the following examples. However, these examples are given for the purpose of illustration and are not to be construed as limiting the scope of the invention. Examples 1-10 and Comparative Examples 1-7

Delivery systems for a teeth whitening ingredient having the following compositions were prepared and purchased.

[Example 1]

. First agent:

Calcium chloride 2%

HPC 3%

TSPP 4%

Urea peroxide 20%

Sodium monofluorophosphate 0.76% Distilled water 70.24%

. Second agent:

Sodium alginate 10%

(Low-viscosity grade)

PVA 10%

Urea peroxide 20%

Distilled water 60%

[Example 2]

. First agent:

Calcium lactate 8%

NaCMC 3%

Sodium perborate 2%

Distilled water 87%

. Second agent:

Sodium alginate 1%

(High-viscosity grade)

PVP (K-90) 10%

Distilled water 89%

[Example 3]

. First agent:

Calcium carbonate 5%

Sodium carbonate 2% Sodium alginate (Manugel DMB) 4%

Distilled water 89% . Second agent:

Sodium alginate (Manugel DMB) 4%

HPMC 5% Acetic acid 5%

SAPP 1%

Hydrogen peroxide 12%

Distilled water 73% [Example 4] . First agent:

Calcium carbonate 5%

Sodium fluoride 0.15%

Sodium alginate (Manugel DMB) 4%

TKPP 2%

Sodium chlorite 2%

Distilled water 86.85%

. Second agent:

Sodium alginate 5%

(Intermediate viscosity)

Gantrez 5%

Micronized PAA hydrogel 3%

Citric acid 3%

Sodium citrate 1%

Vitamin C 0.2%

Distilled water 82.8%

[Example 5]

. First agent:

Calcium carbonate 5%

Sodium percarbonate 18%

Pluronic F127 25%

Vitamin E 0.5%

Distilled water 51.5%

. Second agent:

Sodium alginate 2%

(Low viscosity)

Pluronic F 127 25%

Hydrogen peroxide 6%

Vitamin E 0.5%

Tartaric acid 2%

Distilled water 64.5%

[Example 6]

. First agent: Calcium chloride 2%

PVP 2%

Urea peroxide 16%

TPP 1%

Aerosil 300 6%

Aerosil R972 4%

Distilled water 69%

. Second agent:

Sodium alginate 10%

(Low-viscosity grade)

HPMC 5%

Distilled water 85%

[Example 7]

. First agent:

Calcium lactate 8%

Cab-O-Sil (EH-5) 12%

Sodium perborate 2%

Hydrogen peroxide 3%

Distilled water 75%

. Second agent:

Sodium alginate 1%

(High-viscosity grade)

PVP (K-90) 10%

Distilled water 89%

[Example 8]

. First agent:

Calcium carbonate 6%

Sodium carbonate 2%

Sodium percarbonate 18%

Aerosil 200 15%

Aerosil R812 5%

SAPP 3%

Distilled water 51% . Second agent:

Sodium alginate (Manugel DMB) 4%

HPMC 5%

Carbopol 1% Acetic acid 5%

SAPP 1%

Distilled water 84%

[Example 9]

. First agent:

Calcium carbonate 5%

Sodium fluoride 0.15%

Calcium peroxide 6%

Cab-O-Sil (HS-5) 15%

TKPP 2%

Sodium chlorite 2%

Distilled water 69.85%

. Second agent:

Sodium alginate 5%

(Intermediate- viscosity)

Cab-O-Sil (HS-5) 1%

Gantrez 5%

Micronized PAA hydrogel 3%

Citric acid 3%

Sodium citrate 1%

Vitamin C 0.2%

Distilled water 81.8%

[Example 10]

. First agent:

Calcium carbonate 5%

Sodium percarbonate 9%

Pluronic F 127 25%

Aerosol 300 10%

Vitamin E 0.5% Distilled water 50.5%

. Second agent:

Sodium alginate 2%

(Low viscosity)

Pluronic F127 25%

Vitamin E 0.5%

Tartaric acid 2%

Distilled water 70.5% [Comparative Example 1 ] "NIGHT EFFECTS" (P&G)

Composition: trimethylsiloxy silicate, dimethicone, silicone, sodium percarbonate, sodium bicarbonate, aluminum hydroxide, ethyl acetate, hydrophobic silica, MEK, and flavor [Comparative Example 2] "SIMPLY WHITE NIGHT" (Colgate)

Composition: alcohol, water, urea peroxide, PEG 2M, glycerin, Carbopol, sodium phosphate, and phosphoric acid.

[Comparative Example 3]

. First agent:

Calcium carbonate 5%

Sodium carbonate 2%

Sodium alginate (Manugel DMB) 4%

Distilled water 89%

. Second agent:

Sodium alginate (Manugel DMB) 4%

Acetic acid 5%

SAPP 1%

Hydrogen peroxide 12%

Distilled water 78%

[Comparative Example 4]

. First agent:

Calcium carbonate 5%

Sodium carbonate 2% Distilled water 93%

. Second agent:

HPMC 5%

Acetic acid 5%

SAPP 1%

Hydrogen peroxide 12%

Distilled water 77%

[Comparative Example 5]

. First agent:

Calcium carbonate 6%

Sodium carbonate 2%

Sodium percarbonate 18%

Aerosil 200 15% Aerosil R812 5%

SAPP 3%

Distilled water 51% . Second agent:

Sodium alginate (Manugel DMB) 4% Carbopol 1%

Acetic acid 5%

SAPP 1%

Distilled water 89% [Comparative Example 6]

. First agent:

Calcium carbonate 6%

Sodium carbonate 2%

Sodium percarbonate 18%

Aerosil 200 15%

Aerosil R812 5%

SAPP 3%

Distilled water 51%

. Second agent:

HPMC 5% Carbopol 1%

Acetic acid 5%

SAPP 1%

Distilled water 88%

[Comparative Example 7]

. First agent:

Calcium carbonate 6%

Sodium carbonate 2%

Sodium percarbonate 18%

Sodium alginate 4%

SAPP 3%

Distilled water 67%

. Second agent:

Gantrez 4%

HPMC 5%

Carbopol 1%

Acetic acid 5%

SAPP 1%

Distilled water 84%

* TPP; sodium tripolyphosphate, TKPP; tetrapotassium pyrophosphate, SAPP; sodium acid pyrophosphate

The compositions of Comparative Examples 1 and 2 were indicated on the packages of the respective manufacturers. The composition of Comparative

Example 3 was the same as that of Example 3, except that HPMC, an ingredient for improving the adhesion maintenance to teeth, was not used. The composition of Comparative Example 4 was the same as that of Example 3, except that sodium alginate, an in situ gelling agent, was not added. The composition of Comparative Example 5 was the same as that of Example 8, except that HPMC, an ingredient for improving the adhesion maintenance to teeth, was not used.

The composition of Comparative Example 6 was the same as that of Example 8, except that sodium alginate, an in situ gelling agent, was not added. The composition of Comparative Example 7 was the same as that of Example 8, except that sodium alginate, a thickener, was added to the first agent instead of silica.

[Test Example 1] Evaluation of convenience in use

To evaluate convenience in use, artificial teeth were prepared, and their in vitro characteristics were compared. The artificial teeth were prepared by constituting 96% of the outermost exposed enamel layer of teeth and 60% of the dentin layer positioned under the enamel layer using hydroxyapatite. The teeth were discolored using a solution containing coffee, tea, mucin, etc. Details of the procedure were as follows.

(1) Production of hydroxyapatite (HAP) tablet specimens and discoloration

A hydroxyapatite powder was formed into tablets by means of an IR press, sintered at l,000°C, molded with an epoxy resin, and surface-etched using a strong acid to obtain tablet specimens. The tablet specimens were dipped in a trypticase soybroth (TSB) solution containing tea, coffee, iron and mucin, followed by drying. The dipping and drying were repeated over one week to contaminate the specimens. The specimens were mildly washed under running water with a toothbrush to remove water-soluble and loosely-bound contaminants. Finally, the specimens were dried at room temperature.

The compositions prepared in the examples and comparative examples were applied to the respective discolored specimens. The resulting specimens were allowed to stand at room temperature for one minute to ensure the time taken for the formation of films on teeth. This is because when the compositions are actually applied to teeth, 30 seconds to one minute are taken to form films on the teeth while keeping users' mouth open. Next, the specimens were dipped in water for one minutes, and taken out of the water. This is to determine whether or not the compositions can be maintained on teeth when a large amount of saliva is suddenly secreted in the oral cavity and users drink water. Thereafter, the specimens were softly wiped with a tissue and were confirmed as to whether or not the compositions were sticky and remained on the specimens. This is to confirm whether the films or gels formed on teeth are so sticky to the tongue and other parts of the oral cavity that they give a messy feeling to users, and to confirm how much amount of the compositions remains despite various applied physical stimuli.

Specifically, the compositions prepared in the examples and comparative examples were applied to the HAP tablet specimens, allowed to stand in air at room temperature for one minute, and dipped in water for one minute. After the specimens were taken out of the water, they were wiped with a tissue. It was confirmed as to whether the compositions were sticky and the applied states remained unchanged. Three specimens were used for each test, and the obtained results are shown in Table 1.

Table 1

As can be seen from the data shown in Table 1, the compositions of

Examples 1 to 10 are formulations prepared through in situ gelling of an alginate and showed teeth whitening effects and superior adhesion maintenance to teeth. Particularly, the compositions of Examples 6 to 10 are formulations prepared using a peroxide as a teeth whitening ingredient and silica as a thickener. The composition of Comparative Example 1 is a product currently available under the trade name "Crest Night Effects" from P&G, U.S.A. The composition of Comparative Example 2 is a product currently available under the trade name "Simply White Night" from Colgate. The composition of Comparative Example 3 was the same as that of Example 3, except that HPMC, an ingredient for improving the adhesion maintenance to teeth, was not used. The composition of Comparative Example 4 was the same as that of Example 3, except that sodium alginate was not added. The composition of Comparative Example 5 was the same as that of Example 8, except that HPMC, an ingredient for improving the adhesion maintenance to teeth, was not used. The composition of Comparative Example 6 was the same as that of Example 8, except that sodium alginate was not added.

Stickiness of the compositions to a hand is expressed as "sticky" or "non- sticky" in Table 1. The amount of the compositions remaining on the specimens after dipping and the amount of the compositions remaining on the specimens after wiping the remaining water are expressed as percentages of the area of the compositions remaining on the discolored specimens. When the compositions of the examples and comparative examples were insufficiently gelled for one minute, the compositions were readily dissolved during dipping and considerable amounts of the applied compositions were removed after taking out of the water. Although films were formed, highly water-soluble compositions were readily removed during dipping. In contrast, in the case where

compositions of the examples and comparative examples were applied to the discolored specimens, allowed to stand at room temperature for one minute, and dipped in water for one minute. After the specimens were taken out of the water, they were wiped three times with a tissue. Thereafter, the dry specimens were allowed to stand in a thermo-hygrostat at a temperature of 37°C and a humidity of 95% for 6 hours, and dried at room temperature. L values of the specimens were measured. Difference in the L values, ΔL, before and after the application was calculated for each specimen, and the results are shown in Table 2 below.

Table 2

It appears from Table 2 that since the composition of Comparative Example 1 was highly hydrophobic, the whitening agent was not readily diffused, causing poor whitening effects. Further, since the composition of Comparative Example 4 was highly hydrophilic, it was rapidly diluted with water, leading to poor whitening effects. In contrast, it appears that the composition of Example 3 had superior adhesion maintenance to teeth and was formed into a water-insoluble film, leading to superior whitening effects.

The whitening effects of Example 8 and Comparative Examples 1 and 7 were evaluated immediately after preparation or purchase. The same test was conducted after storage at 40°C for four weeks. The results are shown in Table 3.

Table 3

It appears from Table 3 that since the composition of Comparative

Example 5 11 wwaass highly hydrophobic, the whitening agent was not readily diffused, causing poor whitening effects. It appears that since the composition of Comparative Example 7 showed poor peroxide stability (see, Table 4), it exhibited poor whitening effects. In contrast, since the composition of Example 8 had superior adhesion maintenance to teeth and was formed into a water- insoluble film, it had superior initial whitening effects and superior stability of the peroxide contained in the composition with the passage of time during long-term storage at high temperature.

[Test Example 3] Comparison of peroxide stability after long-term storage at high temperature

The peroxide stability of the compositions prepared in the examples and the comparative examples at a high temperature (4O⁰C) was evaluated in accordance with the following procedure.

(Evaluation of peroxide content in compositions)

First, water was placed in an Erlenmeyer flask. Each of the first agents containing the peroxide was exactly weighed, and completely dissolved. After 5 ml of a 6 N hydrochloric acid solution was added to the flask, about 2g of potassium iodide was dissolved in the mixture. The resulting solution was allowed to stand in a cool and dark place for one hour. The solution was titrated with a 50 mM sodium thiosulfate solution to quantify the peroxide content in the first agent. The results are shown in Table 4 below.

Table 4

The data in Table 4 demonstrate that the peroxide contained in the composition of Comparative Example 7, which was prepared using an alginate having low compatibility with the peroxide as a thickener in the first agent, was readily decomposed during storage at a high temperature, and as a result, the composition showed a very low percentage of remaining peroxide. In contrast, the compositions of Examples 6 and 8, which were prepared using silica highly compatible with the peroxide as a thickener in the respective first agents, showed superior peroxide stability. Industrial Applicability

As apparent from the above description, since the delivery system for a teeth whitening ingredient according to the present invention is a hydrophilic composition that is applied in a liquid form to the surface of teeth, it can be applied to gaps between teeth or irregular teeth. Once the delivery system of the present invention is formed into a water-insoluble film on the surface of teeth, it has superior adhesion to the teeth without being readily dissolved in saliva and moisture present in the oral cavity, thereby ensuring a sufficient contact time between the delivery system and the teeth so that the effective ingredients affect the desired sites. Therefore, the delivery system of the present invention can attain superior whitening effects of the desired level within a short period of time.

That is, since the delivery system of the present invention solves the disadvantages of conventional alginate systems, i.e. poor adhesion and adhesion maintenance to teeth, is convenient and easy to use, and can remain at desired sites for a desired time, it can achieve superior whitening effects of the desired level within a short period of time. In addition, the delivery system of the present invention overcomes the problems of dental treatments using trays and OTC products using strips, i.e. removal or washing of the trays and strips after use, and solves the problems of difficult whitening of sites between teeth and an irregular row of teeth. Furthermore, the delivery system of the present invention solves the drawbacks of spreadable liquid-type OTC products, i.e. rapid dissolution in the moist oral cavity. Moreover, since the delivery system of the present invention is not lipophilic, it offers no messy feeling.

Claims

Claims

1. A liquid delivery system for a teeth whitening ingredient which comprises a first agent containing a water-soluble calcium ion source, and a second agent containing a water-soluble alginate wherein at least one of the first agent and the second agent contains a material for improving adhesion to teeth and a teeth whitening ingredient.

2. A liquid delivery system for a teeth whitening ingredient which comprises a first agent containing a water-insoluble calcium ion source, and a second agent containing an acid capable of causing the water-insoluble calcium ion source of the first agent to generate water-soluble calcium ions wherein at least one of the first agent and the second agent contains a water-soluble alginate, a material for improving adhesion to teeth and a teeth whitening ingredient.

3. A liquid delivery system for a teeth whitening ingredient which comprises a first agent containing a water-soluble calcium ion source, a peroxide and silica, and a second agent containing a water-soluble alginate wherein at least one of the first agent and the second agent contains a material for improving adhesion to teeth.

4. A liquid delivery system for a teeth whitening ingredient which comprises a first agent containing a water-insoluble calcium ion source, a peroxide and silica, and a second agent containing an acid capable of causing the water-insoluble calcium ion source of the first agent to generate water-soluble calcium ions and a water-soluble alginate wherein at least one of the first agent and the second agent contains a material for improving adhesion to teeth.

5. The liquid delivery system according to claim 1 or 3, wherein the water-soluble calcium ion source is at least one selected from calcium chloride, calcium lactate, calcium citrate, calcium aspartate, calcium saccharate, calcium oxovalerate, calcium gluconate, calcium lactobionate and calcium lactogluconate.

6. The liquid delivery system according to claim 2 or 4, wherein the water-insoluble calcium ion source is at least one selected from calcium carbonate, calcium phosphate dibasic (CaHPO₄), barium carbonate and zinc carbonate.

7. The liquid delivery system according to claim 2 or 4, wherein the acid is at least one selected from acetic acid, citric acid, tartaric acid, succinic acid, formic acid, glycolic acid, malonic acid, dichloroacetic acid, oxalic acid, lactic acid, malic acid, gluconic acid, adipic acid, fumaric acid, alginic acid and maleic acid.

8. The liquid delivery system according to claim 1 or 2, wherein the teeth whitening ingredient is at least one selected from peroxides, perborates, percarbonates, peroxyacids, persulfates and metal chlorites.

9. The liquid delivery system according to claim 3 or 4, wherein the peroxide is at least one selected from hydrogen peroxide, carbamide peroxide, calcium peroxide, perborates, percarbonates, peroxyacids and persulfates.

10. The liquid delivery system according to claim 3 or 4, wherein the silica is fumed silica or precipitated silica.

11. The liquid delivery system according to claim 3 or 4, wherein the silica is present in an amount of 0.5% to 30% by weight, based on the first agent.

12. The liquid delivery system according to any one of claims 1 to 4, wherein the water-soluble alginate is sodium alginate which is at least one selected from that of low viscosity, that of intermediate viscosity and that of high viscosity.

13. The liquid delivery system according to any one of claims 1 to 4, wherein the water-soluble alginate has a higher M-block content than G-block content.

14. The liquid delivery system according to any one of claims 1 to 4, wherein the material for improving adhesion to teeth is a polymer having superior adhesion and/or adhesion maintenance to teeth, and is at least one selected from polyvinyl pyrrolidone (PVP), shellac, rosin, polyacrylic acid (PAA), carbopol, carbophil, polysaccharides, polymethyl vinyl ether/maleic acid copolymers (Gantrez), chitosan, hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose (HEC), methyl cellulose (MC), polyox, polyethylene glycol (PEG), poly(N-isopropylacrylamide), poly(N- isopropylacrylamide-co-acrylic acid), poloxamer, pulluran, polyvinyl alcohol (PVA), guar gum, carrageenan, polyacrylate, polyacrylamide, polymethacrylate, polyethacrylate, poly(acrylamide), poly(methacrylate), poly(hydroxyalkylmethacrylate), poly(maleic anhydride), poly(maleate), poly(amide), poly(ethylene amine) and poly(propylene glycol).

15. The liquid delivery system according to claim 14, wherein the material for improving adhesion to teeth is a hydrogel of the polymer or the hydrogel combined with the polymer.

16. The liquid delivery system according to claim 14, wherein the material for improving adhesion to teeth is in the form of a micronized hydrogel powder.

17. The liquid delivery system according to any one of claims 1 to 4, further comprising at least one polyphosphate selected from tetrasodium pyrophosphate (TSPP), sodium acid pyrophosphate (SAPP), sodium tripolyphosphate (STP), sodium potassium pyrophosphate, tetrapotassium pyrophosphate (TKPP), acidic sodium metaphosphate and acidic sodium polyphosphate.

18. The liquid delivery system according to any one of claims 1 to 4, further comprising at least one selected from anticalculus agents, fluoride ion sources, antimicrobial agents, dentinal desensitizing agents, anesthetic agents, antifungal agents, anti-inflammatory agents, H-2 antagonists, anticaries agents, remineralization agents, vitamins and minerals.

19. The liquid delivery system according to any one of claims 1 to 4, wherein at least one of the first agent and the second agents further contains a gel retarder.

20. The liquid delivery system according to claim 19, wherein the gel retarder is at least one selected from sodium hexametaphosphate, tetrasodium pyrophosphate and sodium citrate.

21. The liquid delivery system according to any one of claims 1 to 4, wherein the first agent further contains at least one effervescent selected from sodium carbonate, sodium bicarbonate, calcium carbonate and potassium carbonate.

22. The liquid delivery system according to any one of claims 1 to 4, wherein the first agent is first applied to teeth and then the second agent is applied thereto.

23. The liquid delivery system according to any one of claims 1 to 4, wherein the second agent is first applied to teeth and then the first agent is applied thereto.

24. The liquid delivery system according to any one of claims 1 to 4, wherein a mixture of the first agent and the second agent is applied to teeth.