KR100657127B1 - Delivery system for tooth whitening component using in situ gelling - Google Patents

Abstract

The present invention relates to a tooth whitening component delivery system which is water soluble prior to application to teeth but forms an insoluble film in water by in situ gelling on the oral tooth surface. And a second agent containing at least one of a counter ion salt and a counter ion polymer capable of forming a hydrogel by in situ gelling upon encountering a chitosan of one agent, Liquid tooth whitening component delivery system, characterized in that the substance for improving the adhesion of teeth and the tooth whitening component is contained in at least one of the first agent and the second agent, respectively, because it is insoluble in water and excellent adhesion retention to the teeth or gums It is suitable for the case where short contact time requires sufficient contact time to achieve the desired whitening effect.

Elution gelling, tooth whitening ingredients, water insoluble film, contact time

Description

DELIVERY SYSTEM FOR TOOTH WHITENING COMPONENT USING IN SITU GELLING}

The present invention relates to a tooth whitening component delivery system which is water soluble prior to application to a tooth but forms an insoluble film in water by in situ gelling on the oral tooth surface. The excellent adhesion retention to teeth or gums relates to a tooth whitening component delivery system suitable for applications where sufficient contact time is required to achieve the desired whitening effect with short term use.

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. At-home bleaching products, which use trays tailored to the user's prescription, are most often worn overnight for two weeks. However, due to the inconvenience of having to sleep with a tray every day for two weeks in busy life, many people now prefer in-office bleaching to experience the whitening effect in a single procedure. The technique of reducing the two-week effect by one procedure is generally performed by using a high concentration of 30% to 35% hydrogen peroxide solution, in which case a rubber dam is used to prevent the whitening agent from contacting other than the teeth. You should. Another technique is to use synergistic effects using lasers, heat, or photo activators while using 16% hydrogen peroxide, which is lower than 30-35%. This disposable in-office procedure uses high concentrations of hydrogen peroxide, so the stimulus is high, and retention occurs quickly. In addition, both in-office bleaching and at-home bleaching have a problem that many people are interested but are hard to get the procedure because of the costly and hassle of visiting the dentist.

Accordingly, there is a great demand for a tooth whitening product for over-the-counter (OTC) that is less expensive and can be used alone without a doctor's help and can produce a whitening effect at the level of dental procedures. There are many tooth whitening products that use trays for OTC, which can be purchased at pharmacies or large supermarkets and have a low price. However, OTC products use trays made of a general one-size and shape, so they do not fit well with their teeth and cause irritation caused by the trays. It is known to cause various problems in discomfort and safety due to irritation or leakage of the gel during use. In addition, in most cases it is easy to be noticed by others when attached, it is difficult to use during everyday life and has a disadvantage in that it is difficult to mount for a long time.

In order to solve the drawbacks of tooth whitening products using the trays described above, P & G has applied for a patent on tooth whitening strips (USP), and is the first to commercialize and sell these teeth whitening strips. The tooth whitening strips sold by P & G solve the problem of tray products because the tooth whitening ingredients are applied in a thin and even gel on a thin and flexible polyethylene strip instead of using a tray. to be. However, P & G's product is a wet type, and the adhesive strength between the tooth and the product is not so strong that it can be easily attached and detached, whereas severe impacts such as coughing or There is a disadvantage in that it is not attached to a desired position for a desired time by an operation such as laughing out loud. In addition, since the adhesion of the tooth is poor, foreign matters during attachment are large, and it is not fixed on the teeth, which makes the tooth feel outward, and thus it is not easy to attach it for more than 30 minutes. Moreover, because of the poor adhesion of the teeth on the attachment type, these areas may not be as easy to whiten than other areas, such as those between highly curved teeth or uneven teeth, especially those with severe teeth. There is this.

In 1992, Sintov et al. Disclosed in USP 5,425,953 the use of cellulose-based polymers of low viscosity, soluble in water, as tooth whitening ingredients for film whitening or other dental purposes. It is a liquid formulation that is applied to the teeth and has a low viscosity, which solves the disadvantages of the tray or strip formulation in that it is easy to apply to the tooth sasa or non-uniform teeth. However, since the water-soluble cellulose-based polymer can be diluted or dissolved within 5 minutes in a wet oral cavity, there is a fatal disadvantage that it cannot secure sufficient contact time between the whitening component and the teeth.

In addition, Yue et al. Use organosiloxane in USP 6,569,408, USP 6,589,512, USP 6,692,727 and the like as a method for delivering an effective ingredient to the oral cavity including tooth whitening. Their advantage is that the hydrophobicity is so strong that they are not easily diluted or removed even in a wet oral cavity.However, the hydrophobicity does not easily release hydrophilic drugs, especially strong oxidizing agents, such as tooth whitening agents, which makes it difficult to obtain effects in a short period of time. If you apply it to your teeth, it can give a messy feeling. Accordingly, Moneuze et al. Disclose in US Publication 2004/0037789 the addition of a water soluble gel thickener with an essential concentration of organosiloxane which gives a messy feeling of 10% or less, while containing essentially.

Santarpia et al. Disclose the use of carbomer and poly (ethylene oxide) together in a liquid formulation for whitening teeth in US Publication 2003/0219390. In this case, since the solvent preferably contains 20 to 30% of ethanol, when the surface of the tooth is dried, the liquid is volatilized and the solvent is volatilized to form a film due to the film forming agent poly (ethylene oxide), which is viscous by carbomer. stickiness develops and can remain on the teeth for the desired time. However, depending on the thickness of the ethanol and the dry condition of the tooth and the degree of wetness of the mouth, if the drying time is not sufficient, the desired film may not be formed on the tooth surface, and the poly (ethylene oxide) film is also water-soluble. Because of this, the problem remains that it can be easily diluted or melted by saliva.

Another problem with products using the aforementioned trays and products using strips is that the polymers used in these products generally have a lower viscosity as the temperature rises, so that gels in the oral cavity can be It can flow down without staying on the strip.

In order to solve this problem, Oxman et al. Recently referred to USP 6,312,666 a tooth whitening delivery system using a formulation that is rather viscous at oral temperature. In addition, Oxman et al. Disclosed in USP 6,620,405 a product that solved a problem of difficulty in uniform application of interdental whitening or dentition, which is a disadvantage of conventional trays or strips using these characteristics. Here, we describe a system that can be applied to a tooth with a brush or spray as a liquid with low viscosity before application during storage at room temperature.However, after application to a tooth, the viscosity increases due to intraoral temperature, resulting in a gel with no mobility. have.

All of these viscosity changes due to intraoral application are made using the thermal sensitive property of poloxamer, which is a sol state before gelling temperature and then gels when the gel temperature is higher than gelling temperature. ) Transition occurs. Poloxamers, however, are a good system for already commercialized suppositories, but can be problematic for systems that continue to produce large amounts of saliva, such as the oral cavity. In particular, as the concentration of poloxamer dilutes, the gelation temperature increases, so when the product is applied to the teeth and then diluted with saliva, even after gelation, the gelation temperature becomes high and becomes sol again. Has its drawbacks.

On the other hand, Viegas et al., In USP 5,143,731, 5,346,703 and 6,346,272, contain ionic polysaccharides and essentially ionic polysaccharides, such as poloxamers, and optionally counter ion (which can be crosslinked with such ionic polysaccharides). By adding microencapsulation or ion exchange resins made of heat sensitive materials in potential form, rather than adding counter ions directly, they are liquid at room temperature but semi-solid at body temperature. And a gelling composition having a thermo-irreversible property which is a heat-irreversible gel. This technique also takes advantage of the thermal sensitive properties of the polymer, as disclosed in US Pat. No. 6,312,666, which requires the inclusion of a polyalkylene polymer, such as poloxamer, and is used in suppository, eye drops or intradermal injections. Like this, it can be applied to the part where temperature keeps body temperature all the time and excessive dilution by a large amount of secretion does not occur, but it is applied to teeth or gums in the oral cavity where polymer dilution is easily caused by a large amount of secretion such as saliva. Is inappropriate. In addition, this technique is not suitable for use in systems requiring gelation as soon as possible because the counter ions are supplied by microcapsules or ion exchange resins rather than gelation by the first and second agents.

In consideration of the above points, an object of the present invention is that when applied to a tooth, a liquid having a low viscosity can be easily applied to interdental or uneven teeth, but in the oral cavity, a water-insoluble film is formed to provide excellent retention in the tooth. It is to provide a tooth whitening component delivery system.

In order to achieve the above object, in the present invention, a counter-ion salt which can make a hydrogel by in situ gelling with one agent containing chitosan and chitosan of one agent and It provides a liquid tooth whitening component delivery system consisting of two agents containing at least one of the counter-ion polymer, characterized in that the substance for improving tooth adhesion and the tooth whitening component are contained in at least one of the first agent and the second agent, respectively. do.

The tooth whitening component delivery system according to the present invention is an effective ingredient delivery system in the oral cavity which forms an insoluble gel or film in water through in situ gelling when applied to an oral tooth. In other words, by using in situ gelling of chitosan, which forms an insoluble film on the surface of the tooth within a short time when the first agent and the second agent meet, the gel which is insoluble in water when the chitosan and tripolyphosphate which are water-soluble polymers meet Since the film is formed, there is an advantage of not being much affected by the oral conditions at the time of use such as pH, temperature, amount of water in the oral cavity, and it is characterized in that it is safe to use no organic solvent as a solvent. In addition, such hydrophilic prescriptions are easy to use because they have good applicability when applied to teeth that are also hydrophilic, and avoid the messy feeling that is felt when using hydrophobic prescriptions such as silicone, for example organosiloxane . Moreover, because it contains a polymer with good adhesion retention ability in the oral cavity or gum mucosa, once an insoluble chitosan film or gel is formed in the desired site, it has adhesion retention ability to the desired site in the oral cavity and can be applied to the desired site for the desired time. It is characteristic that we can stay. In addition, since a very thin film is formed, there is no foreign matter, and since it is an edible ingredient, it is not necessary to remove it separately after use.

The tooth whitening component delivery system of the present invention having such features and advantages is easy to use because it is simply applied to the tooth once or twice a day using a brush or a suitable device.

Hereinafter, the tooth whitening component delivery system of the present invention will be described in more detail.

The tooth whitening component delivery system of the present invention is discomfort to be removed after use, which is a disadvantage of a product using a conventional pasting or tray, or lack uniformity (flexibility or elasticity) evenly applied to interdental whitening or teeth It's hard to do that. In addition, the use of a conventional whitening agent overcomes the disadvantages such as rapid dissolution by the saliva of the hydrophilic film formed on the teeth, messy feeling of the lipophilic film, and the release of the whitening component is not easy. This achievement of the system of the present invention is made possible by the creation of a water-insoluble film on the tooth surface after application to the tooth. The advantage is that it is a hydrophilic formulation before application, so it has excellent applicability to the teeth, and after application, it is a water-insoluble film and excellent adhesion retention ability to the teeth, so it can stay in the oral tooth for a desired time, resulting in a whitening effect in a short time. It is possible to obtain sufficient contact time, which is an essential element to obtain.

The greatest advantage of the system of the present invention is that it is particularly suitable as a wet oral whitening component delivery system. Recently, in situ gelling systems using various environmentally sensitive polymers have been introduced as release control systems for active ingredients, but most of them have been used in the body environment which always maintains 37 ° C. It is effective in areas that can be maintained in a dry condition, but it may be a condition where the instantaneous temperature change may vary due to frequent intake of cold drinks or hot foods, such as the mouth, or if there is a constant saliva, especially foreign substances In the case of excessive secretion of saliva is not easy to apply. In addition, in the case of the formulation to be applied to the teeth in the oral cavity, since some may be eaten, the ingredients that can be used are limited. In contrast, the polymer used in the present invention is chitosan, which is a linear polysaccharide generally produced by deacetylation of chitin. Chitin itself is a natural polysaccharide that can be obtained from a variety of sources, and is generally obtained on an industrial scale from shells of crustaceans such as crabs and shrimps, with the advantage that it is a natural polymer and second only to cellulose on earth. Chitosan is non-toxic and environmentally friendly because it has antimicrobial properties, film forming ability, chelating properties and degradation. In addition, because of its physical and chemical properties, it is a safe ingredient commonly used in various medicines and pharmaceutical products, and it is excellent in sensitivity because it uses only water, not an organic solvent, as a solvent. Hydrogel formulations that do not dissolve in water but retain shape while absorbing water have advantages over other polymer systems because they are insoluble in water and hydrophilic, but most have covalently crosslinked networks. This is generally unsuitable for use in oral formulations because it is usually a large number of toxic chemicals. On the other hand, in the present invention, non-covalent crosslinks are used as physical gels, and tripolyphosphate is particularly used as a crosslinker.

In the present invention, a water-insoluble film is a thin film insoluble in water, but has a meaning of including a gel that looks like a film because of its high viscosity and lack of fluidity. In addition, the liquid phase in the present invention means a state in which the fluidity is relatively low viscosity.

Looking at the meaning of in situ gelling in the present invention, once the dictionary meaning of in situ means "in its proper position" as a Latin and Greek idiom, in situ gelling (the desired site) To cause the gel to form at the desired site.

Chitosan is composed of 1,4-beta-linked D-glucosamine and N-acetyl-D-glucosamine residues. The pKa is ˜6.5, which maintains cations at pH 6.5 and below, and is water-soluble, but above pH 6.5. Precipitation starts at, and precipitation occurs around pH 7. It also has a pH-sensitive property, so it can be used as a gelling material for critical pH 7 systems or in body cavities. However, the oral cavity in which teeth whitening, which is the object of the present invention, generally maintains a relatively wide range of pH between pH 6 and 8, and also fluctuates somewhat by drinking or eating an acidic or alkaline beverage or food. It is not a suitable mechanism for the purposes of the present invention. Recently, the degree of purification and deacetylation of chitosan is known for temperature sensitive in situ gelling, which is liquid at room temperature but gelling at body temperature. Unlike other body cavities, the temperature of the tooth is lower than that of 37 ° C, and the temperature is easily changed by external stimuli such as cold or hot drinks. It is not preferred for application to the oral cavity.

Chitosan, on the other hand, is homogeneous or heterogeneous with linear chitosan chains and reagents such as glutaric dialdehyde or ethylene glycol diglycidyl ether (EGDE). Hydrogenes may be made chemically by heterogeneous crosslinking reactions and by gelation upon application. In other words, it may be preferable to apply to oral teeth in this respect, because elution is not caused by external stimulation, but ethylene glycol diglycidyl ether, glutaric aldehyde ( Chemical crosslinkers such as glutaric dialdehyde are not suitable for oral teeth because of their physiological toxicity.

Therefore, due to the nature of the oral conditions as described above, the hydrogel is produced by gelation by the reaction of the first agent and the second agent, not by external stimulation such as pH or temperature, and the mechanism is not chemical crosslinking by chemical components. If it is made by physical crosslinking it will be most suitable for the purpose of the present invention. Furthermore, chitosans have cations in the acidic or neutral vicinity, so that they can meet intermolecular and intramolecular bonds with suitable anions. That is, the amino group of the chitosan as a cation and an anion as the counter ion, such as phosphates, metaphosphates, pyrophosphates, tripolyphosphates, or mixtures thereof, for physical crosslinking Hydrogel is made. Among them, the most common phosphate used for physical crosslinking of chitosan is tripolyphosphate, which is suitable for the present invention. Such gels, using crosslinking chitosan and tripolyphosphate, have been used in microcapsule beads for the delivery of active ingredients in medicine or pharmaceuticals. Since the reaction to make the water-insoluble chitosan gel is caused by the crosslinking of phosphate and chitosan, the concentration of phosphate, the concentration of chitosan, and the molecular weight of chitosan most influence the reaction rate.

Another example in which hydrogels are made by elution rather than external stimulation such as pH or temperature using chitosan is to use polyvalent electrolyte complexes. The concept of a polyvalent electrolyte complex is that obtained by complex formation of two polymers, cation and anion. Chitosan is a variety of natural polyanions such as polyacrylic acid, carbopol, polycarbophil, carboxymethyl cellulose, sodium alginate, alginic acid. Prepared by forming various polyelectrolyte complexes with dextran sulfate, carboxymethyl dextran, heparin, carrageenan, pectin, xanthan or mixtures thereof Can be used.

In addition, a hydrogel suitable for the purpose of the present invention can be obtained by using a counter ion polymer together with a counter ion salt capable of forming gelatinization with chitosan mentioned above. For example, the first agent may contain chitosan, and the second agent may be used as a counterion polymer containing polyphosphate alone or a mixture of polyphosphate and sodium alginate together with the triionic phosphate salt. That is, the counter ion salt may be, for example, one or a mixture of phosphates, metaphosphates, pyrophosphates, tripolyphosphates, and a polyacrylic acid as the counter ion polymer. acid, carbopol, polycarbophil, carboxymethyl cellulose, sodium alginate, alginic acid, dextran sulfate, carboxymethyl dextran One or a mixture of carboxymethyldextran, heparin, carrageenan, pectin, xanthan, or a mixture thereof is simultaneously added to the second agent. This may shorten the gelling time, and may also adjust the mechanical strength of the gel produced by the gelling to the desired level.

Examples using such gelation of chitosan and phosphate on elution are described in US Pat. Nos. 5,318,780, 5,958,443, 6,136,334 and US 2003/0143274. However, they are not intended to overcome the drawbacks of using the collagen shield as a conventional corneal protective device. However, they are not limited to ionic polysaccharides and counters in film forming polymers such as collagen. Medical devices made using physical cross-linking of counter ions, which were intended to increase or decrease the properties of existing gels.

In addition, US Pat. No. 6,638,912 may be cited as the prior art using chitosan in the oral cavity. However, this also does not use gel gelation, but instead of making chitosan into nano-sized fibrous material (fiber) to have improved solubility and activity unlike conventional micro-sized fibrous material (fiber), thereby using hair care (hair care), skin care, odor control, wound care, blood management, sanitary composition, oral care, film formation for film formation, hard surface treatment, fabric treatment, release of hydrophobic and hydrophilic materials, plant care, water purification, drug delivery, etc. It is.

It is an object of the present invention to, unlike these prior arts, utilize gel gelation by physical crosslinking of chitosan to achieve the desired level of tooth whitening effect in a short period of time. In order to achieve the desired level of whitening effect in a short period of time, it is necessary to ensure sufficient contact time between the whitening component having excellent effect and the teeth to be whitened. In general, since chitosan has a cation, it is known that the adhesion to the oral mucosa and the tooth having an anion is somewhat superior to other polymers. However, it is known that it is difficult to secure sufficient adhesive strength to maintain adhesion for a desired time on the surface of the teeth in a humid and moving mouth.

Therefore, the biggest problem to be solved when making a water-insoluble chitosan hydrogel in the oral cavity using chitosan to deliver the tooth whitening component to the teeth may be said to be adhesion retention. In other words, when in situ gelation occurs in chitosan, a water-insoluble film is obtained, but since the chitosan hydrogel has a weak adhesive force, the adhesive itself and the adhesive holding force to the tooth do not exist.

In order to solve this problem, the present invention is intended to complete a tooth whitening component delivery system that is easy to use and can be attached well to a tooth because it is suitable for gelation time. That is, it is preferable to add a polymer which has adhesion to the teeth or adhesion retention and is excellent in compatibility with chitosan and which does not interfere with the in situ gelling mechanism, and more preferably, by adding a polymer. It does not prolong the gelling time. In addition, in consideration of sensitivity and toxicity, water is preferable as the main solvent in the present invention, and therefore, a polymer having excellent solubility in water is preferable. Most preferred polymers are those wherein the side directly contacting the tooth or mucosa increases adhesion and / or adhesion retention, while lacking adhesion on the opposite side.

Polymers suitable for this purpose include polyvinylpyrrolidone (PVP), shellac, rosin, polyacrylic acid (PAA), carbopol, polycarbophil, Polysaccharides, polymethyl vinyl ether / maleic acid copolymers (Gantrez), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC) Hydroxyethyl cellulose (HEC), methyl cellulose (MC), methyl cellulose, polyox, polyethylene glycol (PEG, polyethylene glycol), poly (N-isopropylacrylamide) ), Poly (N-isopropylacrylamide-co-acrylic acid), poloxamer, pullulan, polyvinyl alcohol (PVA, polyvinyl alcohol), Guar gum, ka Carrageenan, polyacrylate, polyacrylamide, polymethacrylate, polyethacrylate, poly (acrylamide), poly (Methacrylate) (poly (methacrylate)), poly (hydroxyalkylmethacrylate) (poly (hydroxyalkylmethacrylate)), poly (maleic anhydride), poly (maleate) (poly ( maleate), poly (amide), poly (ethylene amine) and poly (propylene glycol), or a combination of two or more thereof Although it can be used, preferred is polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), hydroxypropylmethyl cellulose (HPMC), and most preferred is HPMC. These polymers can be used by dissolving them in water, but a hydrogel made by crosslinking can be applied. This hydrogel can be used alone or in combination with these polymers. Hydrogels obtained by crosslinking polymers with excellent adhesion to teeth have the advantage of absorbing water and exerting adhesion, while maintaining the shape without dissolving in water, thereby increasing the retention in wet oral cavity. These hydrogels can also be applied in the form of micronized powders.

In particular, when the thermally sensitive polymers such as poloxamer, poly (N-isopropylacrylamide), and poly (N-isopropylacrylamide-coacrylic acid) are used with chitosan alone or with other polymers, In addition to the increase, the rigidity varies with temperature, so that the gelation temperature of these polymers coincides with the oral temperature, which is relatively higher than room temperature, resulting in a delivery system with better mechanical strength.

In the liquid tooth whitening component delivery system by in situ gelling according to the present invention, 1 is composed of an aqueous solution containing essentially chitosan, and 2 is composed of an aqueous solution containing an anionic salt and / or an anionic polymer. In this case, the polymer for enhancing adhesion to the tooth may be included in any one or both of the first agent and the second agent. In addition, the tooth whitening component may likewise be included in either or both of the first and second agents.

The method of applying the system of the present invention to a tooth can be by any of spray, mouthwash, paste, ointment, gel, liquid and the like. In addition, the first agent and the second agent may be packaged separately in different formulations, or may be two-barrel and one-orifice containers. May be applied to Even if the first agent and the second agent are packaged separately, the mixture may be applied immediately to the desired site after the mixture is prepared immediately before use, but the first agent is first applied to the desired area and then the second agent is applied or the second agent is applied first. One agent can also be apply | coated.

Chitosan, which is essentially contained in the present invention, is applicable to all the various grades that can be used for oral products.

In the system of the present invention, the tooth whitening component is possible as long as it can be applied to the teeth in the oral cavity to produce a whitening effect. As a strong whitening ingredient is effective as a tooth whitening ingredient, it is possible to perform all these functions while being used for oral products. For example, peroxides, perborates, percarbonates, peroxyacids, persulfates, metal chlorites, and the like can be used. Peroxides include, for example, hydrogen peroxide, carbamide peroxide, calcium peroxide, and the like. The most preferred of the percarbonates is sodium percarbonate. Metal chlorite is, for example, calcium chlorite, barium chlorite, magnesium chlorite, lithium chlorite, sodium chlorite, sodium chlorite Potassium chlorite and the like.

In addition, in the present invention, although a peroxide is used as the main whitening agent, condensed phosphate may be used together with the peroxide to improve the whitening effect. Examples of condensed phosphates that can be used include, for example, sodium tetrapyrophosphate (TSPP), sodium pyrophosphate (SAPP), sodium polyphosphate (STP), sodium potassium pyrophosphate ), One or two or more of tetrapotassium pyrophosphate (TKPP), acidic sodium meta-phosphate, and acidic sodium polyphosphate may be used together with the strong oxidizing agent. . In general, condensed phosphates are known to be effective as tartar removal or as an anticalculus agent in toothpaste. In addition, these are excellent metal chelating agents, and since they can effectively remove stains of teeth generated by metals such as iron, calcium, and magnesium in food and working environments, they are known to contribute to the improvement of the whitening effect. Therefore, when these polyphosphates and strong oxidants are used together in the system of the present invention, it is expected to be effective in inhibiting tartar formation or removing tartar as well as improving the whitening effect and prolonging the contact time between the teeth and the polyphosphate. Since these condensed phosphates may react with chitosan and cause gelation upon dissolution, the system of the present invention must be added to a formulation containing no two agents, namely chitosan.

The benefit of being able to stay on for a desired time by applying to the teeth can be effective not only in whitening teeth but also in delivering useful active ingredients in the oral cavity simultaneously or separately. Intraoral active ingredients that can be applied separately or as a tooth whitening component in the system of the present invention include an anticalculus agent, a fluoride ion source, an antimicrobial agent, and a dentin sensitizer. desensitizing agents, anesthetic agents, antifungal agents, antiinflammatory agents, H-2 antagonists, anticaries agents, remineralization agents, vitamins and minerals (vitamins and minerals).

Specific examples of these active ingredients include, but are not limited to, fluoride ions such as sodium fluoride, stannous fluoride, indium fluoride, amine fluoride, and sodium monofluorophosphate. monofluorophosphate). The reminerlaization agent is preferably hydroxyapatite, which is a major component of teeth, but a composition capable of making in situ hydroxyapatite by reaction is also possible. Tartar production inhibitors (anticalculus agent) is capable of chelating calcium ions such as, for example, polyphosphate, pyrophosphate, etc., all of which are effective for whitening teeth. In the present invention, since the foregoing has already been mentioned as the whitening effect enhancing component, detailed description thereof is omitted here. Antimicrobial agents include, for example, triclosan, chlorhexidine, alexidine, hextidine, sanguinarine, benzalkonium chloride, salicylanilide , Domiphen bromide, cetylpyridinium chloride (CPC) and tetradecylpyridinium chloride (TPC) are possible, and essential oils may also be used. Examples of anti-inflammatory agents include aspirin, ketorolac, flurbiprofen, piroxicam, meclofenamic acid, and the like. Vitamins and minerals include, for example, thiamine, riboflavin, nicotinic acid, pantothenic acid, pyridoxine, biotin, folic acid, vitamin B ₁₂ (vitamin B ₁₂ ), lipoic acid (lipoic acid), ascorbic acid (ascorbic acid), vitamin A (vitamin A), vitamin D (vitamin D), vitamin E (vitamin E), vitamin K (vitamin K) and the like. . Coenzymes may also be included.

In situ gelation reaction using chitosan suitable in the tooth whitening delivery system according to the present invention, the shorter the gelation time, the more convenient the consumer. Since it does not use a volatile solvent, it is not necessary to open the mouth more than necessary to dry sufficiently, so it is more convenient than the existing product, but it is important to keep the applied state until gelation is important. Therefore, the time required for gelation is preferably not longer than 5 minutes, preferably within 1 minute, most preferably within 30 seconds. However, this may vary somewhat depending on the method of use, for example, when using two barrels and one-orifice container, one agent and two agent meet once in the container and uniformly Since it has to be applied after it has been applied, it should be designed with the mixing time in mind.

The tooth whitening delivery system according to the present invention is applicable to various formulations, and thus various methods of use are possible. There are many different types of formulations, for example, it can be used as a spray formulation such as hair spray with a low viscosity, by tapping lightly on the desired area such as water, or by using a brush such as nail polish. You can also apply it to your teeth by applying it to a toothbrush, gargle it with a mouthwash, or squeeze through a small hole like a high-end cosmetic. In this case, you can press directly on the tooth to squeeze it, or press it into a separate container or brush and use it.

In addition, in the tooth whitening delivery system of the present invention, one agent and two agents may be used separately. In this case, the method of using the one agent and the second agent may be variously applied. That is, the first agent may be applied to the tooth as a toothpaste formulation using a toothbrush, and the second agent may be brought into contact with the mouthwash via goggles. Of course, it is also possible to use both the first and second agents in the same way using the brush, and various combinations are possible. It is also possible to use a container having two barrels or chambers but one orifice without using the first and second agents separately.

If the system of the present invention consists of one agent and two agents and is packaged separately, one agent or two agents may be first applied to the tooth with a suitable instrument and then two agents or one agent applied thereon. For example, if the formulation is a spray type, it can be sprayed. If the formulation is a liquid with a suitable viscosity, apply it with a brush or a suitable device, and if it is a paste formulation such as toothpaste, apply it to a tooth with a toothbrush or a suitable device. In this case, the film is not formed as the solvent is volatilized, but because the first agent and the second agent meet to form a film, the film is formed within a short time without being affected by intraoral conditions. Since the formed film is an edible ingredient, it can be easily removed during a routine process such as eating food, drinking a drink, or brushing over time without using it separately.

In addition, the system of the present invention may be applied directly to a tooth using a suitable device by using a suitable device without making the first and second agents, respectively, using a device other than the tooth to make a mixture immediately before use. For example, when the first agent and the second agent are contained in a container consisting of a double barrel, one orifice, a mixture is made immediately before use within the container and the mixture exited through the hole is a suitable device. Apply to the tooth through.

As described above, once the film of the tooth whitening delivery system of the present invention is made on the teeth, the adhesion to the teeth is excellent and the water is insoluble, so naturally, the saliva is secreted in the saliva, or something is spontaneously excreted in the oral cavity. Even if it is possible to maintain the desired time at the desired site. The system of the present invention is more effective for the whitening effect if possible not to ingest food or drink until the desired use time after application, but light water or beverage can be ingested, which is more convenient.

In addition, the tooth whitening delivery system according to the present invention does not have a backing layer, so it is safe for overnight use and is also suitable for this. In particular, a relatively small amount of saliva is secreted during sleep, and there is no fear of melting during sleep because there is not much movement in the oral cavity, so sufficient contact time can be secured, which is an advantage that the whitening effect can be seen in a shorter time. In addition, since it is not lipophilic, it does not feel messy, so it is characterized by excellent feeling even if it stays on the teeth for a long time.

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

Examples 1-4 and Comparative Examples 1-4

The tooth whitening component delivery systems of Examples 1-4 and Comparative Examples 1-4 were prepared or purchased with a composition as described below.

Example 1

Agent 1: chitosan 2%

HPMC 3%

Vitamin E 1%

Acetic acid 1%

93% purified water

Part 2: Carbopol 2%

Sodium Tripolyphosphate 10%

Hydrogen peroxide 6%

Purified Water 82%

Example 2

Agent 1: chitosan 1%

Urea peroxide 15%

PVP 10%

Acetic acid 1%

Purified Water 73%

2nd agent: Carboxymethyl cellulose 3%

Sodium Tripolyphosphate 5%

Sodium Pyrophosphate 4%

Purified water 88%

Example 3

Agent 1: chitosan 5%

Micronized PAA Hydrogel 3%

Citric acid 3%

89% purified water

2nd agent: 30% of polyacrylic acid

Sodium pyrophosphate 5%

Percarbonate 18%

Purified Water 47%

Example 4

Agent 1: chitosan 2%

Poloxamer (Pluronic F-127) 20%

Tartaric acid 2%

Vitamin C 0.2%

Purified water 75.8%

2nd agent: Sodium alginate 3%

Xanthan Gum 1%

Polyvinyl Alcohol 10%

Sodium chlorite 1%

Purified water 85%

[Comparative Example 1] P & G's "NIGHT EFFECTS"

Composition: Trimethylsiloxy silicate, Dimethicone, Silicone, Sodium Carbonate Peroxide, Sodium Bicarbonate, Aluminum Hydroxide, Ethyl Acetate, Hydrophobic Hydrodrophobic Silica, MEK, Fragrance

[Comparative Example 2] Colgate's "SIMPLY WHITE NIGHT"

Composition: Alcohol, Water, Urea Peroxide, PEG 2M, Glycerin, Carbopol, Sodium Phosphate, Phosphoric Acid

Comparative Example 3

Agent 1: chitosan 2%

Vitamin E 1%

Acetic acid 1%

Purified water 96%

2nd agent: Sodium tripolyphosphate 10%

Hydrogen peroxide 6%

Purified water 84%

[Comparative Example 4]

Chapter 1: HPMC 3%

Vitamin E 1%

Acetic acid 1%

95% purified water

Part 2: Carbopol 2%

Sodium Tripolyphosphate 10%

Hydrogen peroxide 6%

Purified Water 82%

Sodium tripolyphosphate; sodium tripolyphosphate, acidic pyrophosphate; sodium acid pyrophosphate

The compositions of Comparative Examples 1 and 2 were quoted as they were indicated by the manufacturer on the packaging of each product. In Comparative Example 3, all of the other compositions were the same as in Example 3, but did not use the first HPMC and the second carbopol, which are components for improving adhesion and holding strength. In Comparative Example 4, the other composition is similar to Example 3, but only chitosan, which is an in situ gelling agent, is not added.

Experimental Example 1 Evaluation of Usability

To evaluate the ease of use, artificial teeth were made and compared in vitro conditions. Artificial teeth consisted of hydroxyapatite, which constitutes 96% of the enamel (enamel) exposed to the outermost part of the tooth, and 60% of the dentin (dentin) immediately below it. In addition, teeth were colored using a solution containing coffee, tea, mucin, etc., which are the main causes of tooth coloring. The detailed method is as follows.

(1) Hydroxyapatite (HAP) Tablet Specimen Preparation and Coloring Method

Tablets of hydroxyapatite powder were made by IR press and sintered at 1000 ° C, then molded with epoxy resin to make a resin, and the surface was etched with strong acid, and then the specimen was dissolved in a solution of trypticase soybroth (TSB) dissolved in tea, coffee, iron and mucin. The process of soaking and drying was repeated and the operation was contaminated for 1 week. The contaminated specimens were washed lightly with a toothbrush in running water to remove contaminants that were easily dissolved or removed by water, and then dried at room temperature.

The colored specimens thus prepared were coated with the solutions prepared in Examples and Comparative Examples, respectively, and left to stand at room temperature for 1 minute. This is to give a time to keep the mouth closed in 30 seconds to 1 minute in order to ensure the time to form a film on the tooth when applied to the actual tooth, which is intended to reproduce this. Next, after dipping in water for 1 minute, it was taken out of the water again. This is to check whether it can be kept on the teeth when suddenly excessive saliva is secreted in the mouth with a lot of saliva secretion or when the user is consuming water. Removed from the water again and wiped lightly with a tissue, and then confirmed the stickiness and the degree remaining on the teeth. This is because the film or gel on the surface of the tongue or other parts of the oral cavity, the stickiness is so large that it can give a messy feeling, it is also a process to check whether it can remain in various physical stimuli.

That is, the liquid prepared in each of Examples and Comparative Examples was applied to the HAP tablet specimens, left for 1 minute in air at room temperature, dipping in water for 1 minute and then taken out to remove water with a tissue, and then there was a stickiness, In this process, it was compared whether it was kept as applied. Three specimens each were tested and the results are shown in Table 1.

Sticking to hands after 1 minute at room temperature How much remains in the specimen after dipping How much remains after draining with tissue paper Stickiness to hand after removing water Example 1 Not sticky 100% 100% Not sticky Example 2 Not sticky 100% 100% Not sticky Example 3 Not sticky 100% 100% Not sticky Example 4 Not sticky 100% 100% Not sticky Comparative Example 2 Not sticky 0% 0% Not sticky Comparative Example 3 Not sticky 100% 0% Not sticky

In Table 1, Examples 1 to 4 are tooth whitening formulations having excellent adhesion retention to teeth while using in situ gelling of chitosan, and Comparative Example 2 uses Simply White Night of Colgate. In Comparative Example 3, all other compositions were the same as in Example 3, but only the carbopol was used in the HPMC and the second agent as the component for improving the adhesive holding power.

Here, if there is stickiness, it is marked as "Sticky", if not, "Non-Sticky", and the degree of remaining on the specimen after dipping and the amount remaining after removing water with a tissue is displayed on the colored specimen. The remaining area is expressed as a percentage. When the gelation time of Example or Comparative Example was not enough for 1 minute, it was easily melted during dipping and removed from the water, and a significant amount of the applied amount was removed, and even if a film was formed, the solubility in water was large. In case it could be easily removed in the dipping process. Conversely, even if there was some adhesion to the HAP tablet specimens, if the resulting film or gel was sticky, the gel would easily be removed from the HAP tablet surface as it touched the hand or tissue when touched or touched by a tissue to remove water. If the film formed on the teeth is sticky, the patch type that is applied is not a problem because there is a back layer that is insoluble in water. This is not a desirable feature.

Experimental Example 2 Comparison of Whitening Effect

The whitening effect of the solutions prepared in Examples and Comparative Examples was evaluated in vitro, using colored hydroxyapatite (HAP) tablet specimens prepared in the same manner as in Experimental Example 1 above. That is, the liquid prepared in Examples and Comparative Examples was applied onto the colored specimens and left at room temperature for 1 minute, and then dipping in water for 1 minute and then gently wiped three times with a tissue, and then the temperature was 37 ° C., After leaving for 6 hours in a thermo-hygrostat set to 95% humidity and drying at room temperature, the L value was measured. ΔL, which is the difference between L values before and after application, is calculated and shown in Table 2 below.

ΔL (after 1 hour 6 hours attachment) Example 1 35.10 ± 1.80 Comparative Example 1 15.75 ± 1.98 Comparative Example 4 16.30 ± 1.20

In Table 2, Comparative Example 1 is very hydrophobic, so that the whitening agent is not easily released, and the whitening effect appears to be somewhat reduced, while Comparative Example 4 is hydrophilic and is easily diluted with water, thereby decreasing the whitening effect. On the other hand, Example 1 seems to have an excellent whitening effect because it has a water insoluble film while also having excellent dental adhesion.

As described above, the tooth whitening component delivery system according to the present invention is applied to the surface of the tooth in a liquid form as a hydrophilic formulation is easy to apply to the gap between the teeth and can be easily applied even when the teeth are uneven, Once the water-insoluble film is formed on the surface of the teeth, it is not easily melted by saliva or moisture in the oral cavity, and excellent adhesion of the teeth allows sufficient contact time to ensure that the active ingredient can act in the desired area. Whitening effect can be obtained.

That is, the tooth whitening component delivery system of the present invention is sufficiently easy to use by improving the tooth adhesion and adhesion retention strength than the conventional gelling system itself using the chitosan, it is easy to use, and can stay for a desired time in the desired area in the oral cavity Therefore, the desired level of whitening effect can be obtained for short term use. To solve the problem of dental treatments using trays or OTC products using trays and strips, the hassle that needs to be removed or cleaned after use, or it is difficult to whiten evenly if the interdental whitening or dentition is uneven. In addition, it solves the problem of dissolving easily in a wet oral cavity, which is a disadvantage of the liquid type OTC product, but it is not messy because it is not lipophilic.

Claims (13)

1 agent containing chitosan, 2 containing at least one counter ion salt and counter ion polymer which can meet with the chitosan of one agent and form a hydrogel by gelation in situ gelling A liquid tooth whitening component delivery system, comprising: zero, and a substance and a tooth whitening component for improving tooth adhesion are contained in one or two agents, or both. The method of claim 1, wherein the counter-ion salt is at least one selected from the group consisting of phosphates, metaphosphates, pyrophosphates and tripolyphosphates (liquid tooth whitening component delivery) system. 3. A liquid tooth whitening component delivery system according to claim 2, wherein the counter ion salt is tripolyphosphate. The method of claim 1, wherein the counter ion polymer is polyacrylic acid, carbopol, polycarbophil, carboxymethyl cellulose, sodium alginate, alginic acid. , Dextran sulfate, carboxymethyl dextran, carboxymethyl dextran, heparin, carrageenan, carrageenan, pectin, and xanthan. Liquid tooth whitening component delivery system. The method of claim 1, wherein the material for improving tooth adhesion is a polymer, polyvinylpyrrolidone (PVP, polyvinyl pyrrolidone), shellac (rosac), rosin (polyacrylic acid), polyacrylic acid (PAA, polyacrylic acid), carbopol ( carbopol, polycarbophil, polysaccharides, polymethyl vinyl ether / maleic acid copolymers (Gantrez), hydroxypropyl cellulose (HPC), hydroxypropyl Methyl cellulose (HPMC, hydroxypropylmethyl cellulose), hydroxyethyl cellulose (HEC, hydroxyethyl cellulose), methyl cellulose (MC, methyl cellulose), polyox, polyethylene glycol (PEG, polyethylene glycol), poly (N-isopropyl) Acrylamide) (poly (N-isopropylacrylamide)), poly (N-isopropylacrylamide-coacrylic acid) (poly (N-isopropylacrylamide-co-acrylic acid)), poloxamer, pullulan, Polyvinyl alcohol (PVA, po lyvinyl alcohol, guar gum, carrageenan, polyacrylate, polyacrylamide, polymethacrylate, polyethacrylate, polyethacrylate Amide (poly (acrylamide)), poly (methacrylate), poly (hydroxyalkylmethacrylate), poly (maleic anhydride) ), Poly (maleate), poly (amide), poly (ethylene amine) and poly (propylene glycol) Liquid type tooth whitening component delivery system, characterized in that at least one member selected from the group consisting of. The liquid tooth whitening component delivery system according to claim 5, wherein the material for improving tooth adhesion is a hydrogel of the polymer alone or in combination with a polymer. The liquid tooth whitening component delivery system according to claim 5 or 6, wherein the material for improving tooth adhesion is micronized by powdering the hydrogel of the polymer. The tooth whitening component of claim 1, wherein the tooth whitening component is an oxidizing agent, wherein the peroxide, perborate, percarbonate, peroxyacids, persulfates, and metal chlorites Liquid type tooth whitening component delivery system, characterized in that at least one selected from the group consisting of. The method of claim 1, wherein as condensation phosphate, sodium pyrophosphate (TSPP), sodium pyrophosphate (SAPP), sodium polypolyphosphate (STP), sodium potassium pyrophosphate In addition, the at least one selected from the group consisting of tetrapotassium pyrophosphate (TKPP), acidic sodium meta-phosphate and acidic sodium polyphosphate is further included in the second agent. Liquid tooth whitening component delivery system, characterized in that. 2. The method of claim 1, wherein the antitumor forming agent (anticalculus agent), fluoride ion source, antimicrobial agents, dentin desensitizing agent, anesthetic agent, antifungal agent ), At least one selected from the group consisting of antiinflammatory agents, H-2 antagonists, anticancer agents, remineralization agents, vitamins and minerals Liquid tooth whitening component delivery system, characterized in that it further comprises. 2. A liquid tooth whitening component delivery system according to claim 1, wherein the first agent is first applied to the tooth and then the second agent is applied thereon. 2. A liquid tooth whitening component delivery system according to claim 1, wherein the second agent is first applied to the tooth and then the first agent is applied thereon. 2. A liquid tooth whitening component delivery system according to claim 1, wherein the first and second agents are made into a mixture and then applied to the teeth.