JP6077149B2 - Dentifrice composition for periodontal disease - Google Patents

Description

  The present invention relates to a dentifrice composition for periodontal disease containing a medicinal component.

  Dentifrice compositions include those in which active ingredients such as various medicinal ingredients, flavors, and pigments are encapsulated in capsules. As such a capsule-containing dentifrice composition, an opaque microcapsule formed by depositing an insoluble salt as if covering the capsule film in a state where at least a part thereof is buried in a capsule film whose core substance is a colored oily substance (patent Containing an opaque microcapsule encapsulating a pigment as in Document 1); comprising a dentifrice filled with a scented material (Patent Document 2), a flavor in granular form and a matrix encapsulating it A self-fluxing granular delivery system (Patent Document 3) for imparting enhanced flavor and sweetness to a food composition, a flavor-encapsulating cyclodextrin granule coated with a coating material comprising shellac, glycerin fatty acid ester and excipients; Of a granular dentifrice composition (Patent Document 4) with a change in flavor formed by mixing a granular dentifrice base Containing capsules encapsulating sea urchin flavor components; fine particles obtained by dispersing a water-soluble medicinal solid powder in a core-forming thermoplastic resin or high melting point wax-like substance, core-forming thermoplastic resin or high Toothpaste (Patent Document 5) containing fine capsules coated with a high-melting wax-like substance for coating, which has a lower melting point than that of the melting-point wax-like substance, and water-soluble drugs such as vitamins, herbal medicines and extracts thereof as a core substance. A capsule encapsulating a medicinal ingredient such as a double capsule coated with a lipophilic substance such as a wax-like substance and further coated with a hydrophilic substance such as gelatin and a dentifrice composition (Patent Document 6) containing the same. What is contained is known. It is also known to use capsules with specific particle size and specific strength in combination with water-insoluble granules for the purpose of easily destroying capsules by normal brushing while preventing breakage of capsules during production. (Patent Document 7).

  The purpose of blending capsules in these conventional dentifrice compositions is to improve the stability of the active ingredients and disintegrate the capsules in the mouth to release medicinal ingredients, flavoring agents, pigments, etc. in the mouth, The effect of these components is to be expressed throughout the oral cavity.

  Periodontal disease, on the other hand, causes chronic inflammation in periodontal tissues due to stimulation of bacterial bacterial endotoxin (lipopolysaccharide: LPS) and lipoproteins, and periodontal pockets are formed in the gingival crevice. Is a disease in which the teeth eventually fall out due to absorption by the alveolar bone. Unlike gingivitis, which is relatively easy to recover by removing plaque by appropriate brushing etc., periodontal disease is difficult to recover by removing plaque alone, and it is necessary to deliver a medicinal component directly to the gingival crevice . However, even if a dentifrice composition or a mouthwash is used, there is a problem that the delivery of medicinal ingredients to the gingival crevice is low (for example, see Non-Patent Document 1), and tools and containers that are directly injected into the gingival crevice have been developed. However, there is a need for improved techniques for efficiently delivering medicinal ingredients to the gingival crevice.

Japanese Patent Publication No. 63-48580 JP-A-49-453 JP-A-1-193216 Japanese Patent Publication No. 5-58404 Japanese Patent Publication No. 50-25011 JP 61-225115 A JP-A-8-169813

Clin.Periodontol. 19: 340-344,1992

Even if a dentifrice composition containing conventional capsules is used, the capsules are easily disintegrated in the oral cavity by brushing and disperse the medicinal ingredients throughout the oral cavity, making it difficult for the capsules to be delivered to the gingival crevice In addition, it was found that even when delivered to the gingival crevice, the capsule is not easily broken, and it is difficult to cause the medicinal component to act directly on the gingival crevice. In addition, since conventional capsules are blended into a dentifrice composition using a means for improving the strength such as thickening the film, there is also a problem that the film remains in the mouth after the teeth are brushed and the usability is not good. .
Accordingly, an object of the present invention is to provide a dentifrice composition capable of delivering a medicinal component to the gingival crevice and allowing the medicinal component to act efficiently in the gingival crevice.

Then, as a result of studying the above problems, the present inventors have incorporated hydrogel particles having an average particle diameter of 50 to 500 μm containing medicinal ingredients into the dentifrice composition, so that the hydrogel particles are gingival by brushing. It has been found that a dentifrice composition that is delivered to the groove and destroyed in the gingival sulcus, the medicinal component acts efficiently in the gingival sulcus, and has a good feeling of use.
That is, the present invention provides a dentifrice composition for periodontal disease containing (A) a hydrogel particle having an average particle diameter of 50 to 500 μm, (B) a binder, and (C) water, which contains a medicinal component. To do.

  The dentifrice composition of the present invention is useful for the prevention and improvement of periodontal disease and has a good feeling of use because the medicinal component efficiently acts in the gingival crevice.

It is a conceptual diagram of the tooth model 1 for evaluating the delivery property of the hydrogel particle and medicinal component to a gingival crevice. It is a figure which shows the delivery rate to a gingival crevice of a medicinal ingredient. It is a figure which shows a mode that a hydrogel particle enters the inside (below boundary P) of the gingival crevice model 14. FIG.

[Hydrogel particles]
The hydrogel particles contained in the dentifrice composition of the present invention contain medicinal ingredients in a dispersed state or an emulsified state. As a medicinal component, what is necessary is just to have a prevention or improvement effect with respect to periodontal disease, and an anti-inflammatory agent, a blood circulation promoter, an antibacterial agent, a bactericidal agent, a hemostatic agent, an antioxidant, etc. are mentioned. These medicinal components may be oil-soluble or water-soluble. If oil-soluble medicinal components are dissolved in a solvent (oil agent), and if they are water-soluble medicinal components, they are insoluble in water by mixing with a polymer, for example. These composites can be formed and dispersed in the hydrogel particles.

  In the present specification, the “hydrogel” is a water-containing swollen body formed by blending a gel-forming agent with water as a solvent, which is insoluble in water, and a polymer as the gel-forming agent. A natural polymer compound is preferable. The hydrogel particles preferably have no coating covering the hydrogel, and in the hydrogel, an oil-soluble medicinal component dissolved in an oil agent, or a water-soluble medicinal component and a water-soluble polymer formed a complex. Those in which the product is dispersed are preferred.

  Oil-soluble medicinal ingredients are not particularly limited, but azulenes, tocopherols, glycyrrhetinic acids, triclosan, isopropylmethylphenol, hinokitiol, dihydrocholesterol, dihydroabietic acid, etc., which are known to be effective in preventing and improving periodontal disease These may be used alone or in admixture of two or more. Examples of the azulene used in the present invention include azulene and guaiazulene. Examples of the tocopherol include dl-α-tocopherol acetate and tocopherol nicotinate. Examples of the glycyrrhetinic acid include α-glycyrrhetinic acid and β. -Glycyrrhetinic acid, glycyrrhizic acid, etc. are mentioned, β-glycyrrhetinic acid is preferred.

  The content of the oil-soluble medicinal component in the hydrogel particles used in the present invention is such that the oil-soluble medicinal component sufficiently acts on the gums, and from the viewpoint of the stability of the hydrogel particles, the total weight of the hydrogel particles Is preferably 0.01 to 10% by mass, more preferably 0.1 to 2% by mass.

The solvent of these oil-soluble medicinal ingredients is not limited as long as it is an oil that is liquid at room temperature (25 ° C.). For example, fatty acid ester oils such as isopropyl myristate and isopropyl palmitate, neopentyl glycol dicaprate, fatty acid Examples thereof include liquid triglycerides such as (C ₈ , C ₁₀ ) triglycerides.

  The content of the oil agent as the solvent of the oil-soluble medicinal component in the hydrogel particles used in the present invention is the total weight of the hydrogel particles from the viewpoint of dissolving the oil-soluble medicinal component and the stability of the hydrogel particles. As a reference | standard, 0.1-50 mass% is preferable, and 0.5-10 mass% is more preferable.

When an oil-soluble medicinal ingredient is used as the medicinal ingredient, the hydrogel particles should contain a dispersant or an emulsifier so that the oil-soluble medicinal ingredient and the solvent (oil agent) can exist stably in a dispersed or emulsified state. Is preferred.
Examples of the dispersant or emulsifier include one or more selected from the group consisting of a polymer emulsifying dispersant, a nonionic surfactant, an anionic surfactant, a cationic surfactant, and an amphoteric surfactant.
The concentration of the dispersant and the emulsifier is 0.001 to 10% by mass, more preferably 0.005 to 5% by mass, particularly 0.01 to 5%, based on the total weight of the hydrogel particles from the viewpoint of uniformly dispersing the oil-soluble medicinal component. 2% by mass is preferred.

Examples of the polymer emulsifying dispersant include, for example, acrylic acid / alkyl methacrylate copolymer (trade name: Pemlen TR-2, etc., manufactured by Noveon), polyvinylpyrrolidone, polyvinyl alcohol and derivatives thereof, polyacrylamide, and alkylphenol formaldehyde condensate. And synthetic polymer compounds such as ethylene oxide adducts, natural polymer compounds such as lecithin derivatives, starch derivatives, casein, and gum arabic. Of these, acrylic acid / alkyl methacrylate copolymers are preferred.
Examples of the anionic surfactant include acyl amino acid salts such as sodium acyl glutamate and acyl sarcosine sodium, alkyl phosphates such as sodium alkyl phosphate, alkyl sulfate salts, higher fatty acid sulfonated monoglyceride salts, fatty acid esters of isethionic acid. Salt, N-methyl long chain acyl taurine sodium salt, polyoxyethylene monoalkyl phosphate and the like.

  Examples of the nonionic surfactant include sucrose fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, and the like.

In the case of a water-soluble medicinal ingredient, it is not particularly limited, but in order to keep it stably in the hydrogel particles in the dentifrice composition using water as a dispersion medium, other ingredients include a water-soluble medicinal ingredient and water. A polymer that forms an insoluble complex (hereinafter referred to as “polymer A”) is preferred. Here, examples of the polymer A include water-insoluble polymers such as polyvinylpolypyrrolidone and water-soluble polymers such as polyvinylpyrrolidone, but water-soluble polymer A is preferable.
Specifically, polyphenols are preferable as the water-soluble medicinal component. The polyphenols can be contained in hydrogel particles by forming a water-insoluble complex with polymer A.

Examples of polyphenols used in the present invention include monomers and oligomers such as condensed tannins and hydrolyzed tannins, in addition to condensed tannin monomers such as catechins, flavanols, flavones, anthocyanidins, and leucoanthocyanidins. And condensed tannin oligomers such as proanthocyanidins, and hydrolyzable tannins such as galloylglucose.
Examples of the catechins include non-epimeric catechins such as catechin, gallocatechin, catechin gallate, and gallocatechin gallate; epicatechins such as epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate. Examples of flavanols include kaempferol, quercetin, myricetin and the like. Examples of flavones include abigenin, steoline, diosmethine and the like. Examples of leucoanthocyanidins include flavan-3-ol and flavan-3,4-diol, and examples of anthocyanidins include cyanidin and delphinidin. Proanthocyanidins is a generic name for oligomers of condensed tannins. Representative examples include oolong tea polyphenol, black tea polyphenol, grape seed polyphenol, pine bark polyphenol, hop polyphenol, apple polyphenol, cranberry polyphenol, blueberry polyphenol, peanut astringent polyphenol, black bean Examples include polyphenols, cacao polyphenols, and salmon tannins.

As polyphenols used in the present invention, catechins and proanthocyanidins are more preferable.
Catechins can be obtained by concentrating and purifying a green tea extract extracted from tea leaves with hot water or a water-soluble organic solvent. In addition, by using green tea extract concentrates such as commercially available Mitsui Norin Co., Ltd. “Polyphenone”, ITO EN Co., Ltd. “Theafuran”, Taiyo Kagaku Co., Ltd. “Sunphenon”, etc., by adjusting the components, A catechin suitable for the purpose can be obtained.
Proanthocyanidins are contained in various plants and fruits.For example, fermented tea leaves, grape seeds, pine bark, hops, apples, cranberries, blueberries, peanut astringents, black beans, cacao, strawberries etc. with water or water-soluble organic solvents. The extracted plant extract can be obtained by concentration, purification or the like. In addition, Maruzen Pharmaceutical “Oolong Tea Extract”, Kenko Tsusho “Matsubark Extract”, “Grape Seed Extract”, “Cranberry Powder”, Asahi Breweries “Applephenon”, Release Science Industry “ Proanthocyanidins suitable for the purpose of the present invention can be obtained by adjusting the components using a concentrate of a plant extract such as “Pancil”.

  The polymer A used in the present invention is not particularly limited as long as it is a polymer that forms a water-insoluble complex with a water-soluble medicinal component. A water-insoluble complex is a substance that precipitates out of water as an insoluble substance when an aqueous solution of a water-soluble medicinal component and polymer A or an aqueous solution of polymer A are mixed. Precipitation of the water-insoluble complex can be confirmed by the turbidity of the mixed solution or the presence of a peak derived from the water-insoluble complex when the mixed solution is measured with a laser diffraction / scattering particle size distribution analyzer. . In addition, the water-insoluble complex includes, for example, those that gradually dissolve when applied to the oral cavity.

Examples of the water-insoluble polymer A include polyvinyl polypyrrolidone (crosslinked polyvinyl pyrrolidone, crospovidone). Examples of the water-soluble polymer A include polyvinyl pyrrolidone polymers, polyvinyl alcohol, water-soluble cellulose ether, polyethylene glycol, polypropylene glycol and the like. As the polyvinylidone polymer, polyvinylpyrrolidone (hereinafter sometimes abbreviated as PVP) is preferable. Examples of the water-soluble cellulose ether include carboxymethyl cellulose, methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl methyl cellulose, and the like, and hydroxyethyl cellulose and hydroxypropyl cellulose are more preferable.
The weight average molecular weight of the polymer A is preferably 6,000 or more, more preferably 60,000 or more, still more preferably 400,000 or more, from the viewpoint of effectively suppressing discoloration of a water-soluble medicinal component such as polyphenols. 1,200,000 or more is particularly preferable. Further, from the viewpoint of suppressing the water-insoluble complex from becoming agglomerated aggregates and obtaining a fine water-insoluble complex, it is preferably 3,000,000 or less, more preferably 2,000,000 or less.
In the present invention, the weight average molecular weight of the polymer A is a value measured by a viscosity method which is a general weight average molecular weight measurement method. The weight average molecular weight can also be measured by a light scattering method or the like. In the present invention, when the polymer A is polyvinylpyrrolidone, the weight average molecular weight is determined by the K-value calculated from the measured viscosity value based on the Fikentscher formula.

  The content of the water-soluble medicinal component in the hydrogel particles used in the present invention is such that the water-soluble medicinal component sufficiently acts on the gingival sulcus and from the viewpoint of the stability of the hydrogel particles, 0.001-10 mass% is preferable on the basis of weight, 0.001-6 mass% is more preferable, and 0.01-3 mass% is still more preferable. The content of the polymer A is preferably 1 to 10 times by mass, more preferably 1 to 8 times by mass with respect to the water-soluble medicinal component, from the viewpoint of effectively suppressing discoloration of the water-soluble medicinal component, for example, polyphenols. 1 to 4 times by mass is preferable.

  In addition, the content of the water-insoluble complex in the hydrogel particles is 0.01% by mass or more, more preferably 0.05 from the viewpoint of obtaining a fine complex by suppressing the complex from becoming agglomerated aggregates. The upper limit is preferably 12% by mass or less, more preferably 8% by mass or less, and further preferably 6% by mass or less.

In the present invention, examples of the gel forming agent used for the hydrogel particles include seaweed extracts such as agar, κ-carrageenan, ι-carrageenan, λ-carrageenan, furseleran, alginate, propylene glycol alginate; guar gum, locust Plant seed sticky substances such as bean gum, tamarind seed polysaccharide, tara gum and cassia gum; Plant fruit sticky substances such as pectin and arabinogalactan; Animal protein such as gelatin, albumin and casein; plant protein such as soy protein and wheat protein; cellulose such as microcrystalline cellulose and derivatives thereof; starch such as starch, starch phosphate ester and starch glycolate and derivatives thereof The recited These may be used alone or in admixture of two or more thereof. As the polymer that forms brittle gel particles that are easily broken physically, κ-carrageenan, agar, and duran gum are preferable.
The content of the gel-forming agent in the hydrogel particles of the present invention is preferably from 0.25 to 5% by mass, preferably from 0.5 to 4 from the viewpoint of preventing breakage when the hydrogel particles are blended into the dentifrice composition. The mass% is more preferable, and 1-4 mass% is still more preferable.

The hydrogel particles in the present invention include a water-soluble medicinal component and polymer A, an oil-soluble medicinal component and a solvent, a gel-forming agent and water, water-soluble organic compounds such as sugars and polyhydric alcohols, colorants, preservatives, Components such as water-soluble fragrances may be contained.
Examples of the saccharide include glucose, galactose, fructose, mannose, mannitol, saccharose, maltose, lactose and the like.
Examples of the polyhydric alcohol include glycerin, sorbitol, ethylene glycol, propylene glycol, and oligosaccharide.

  Although the manufacturing method of the hydrogel particle in this invention is not specifically limited, For example, gel formation agents, such as agar, are mixed with ion-exchange water, and it heats to the temperature beyond the melting temperature of a gel formation agent, and fully dissolves. When an oil-soluble medicinal ingredient is used, the oil-soluble medicinal ingredient and a solvent are mixed here, preferably including a dispersant or / and an emulsifier, for example, a homomixer, etc. Alternatively, hydrogel particles that are cooled and solidified from the melting temperature of the gel-forming agent are obtained by a stirring method or the like. On the other hand, the hydrogel particles containing a water-soluble medicinal component are sufficiently mixed with polymer A and ion-exchanged water together with a gel-forming agent such as agar and heated to a temperature equal to or higher than the melting temperature of the gel-forming agent. Dissolve. After adding and mixing an aqueous solution of a water-soluble medicinal component, hydrogel particles can be obtained by a general dropping method, spraying method, stirring method or the like.

  The dripping method uses the property that a liquid mixture is discharged from a hole and the discharged liquid mixture becomes droplets due to its surface tension or interfacial tension, and the liquid droplets are cooled in a gas phase or liquid phase such as air. This is a method for producing hydrogel particles by solidification. In addition, it is preferable to give a vibration to the liquid mixture discharged from the hole from the viewpoint of producing hydrogel particles having a uniform particle size.

  The spraying method uses a spray nozzle, sprays the liquid mixture from the spray nozzle into the gas phase, forms droplets by the surface tension, and cools and solidifies the droplets in the gas phase to produce hydrogel particles. It is.

  In the stirring method, the mixed liquid is poured into a liquid that has a property that does not substantially mix with the mixed liquid and is adjusted to a temperature equal to or higher than the gelling temperature, and the mixed liquid is atomized by a shearing force by stirring. This is a method for producing hydrogel particles by utilizing the property of forming droplets and cooling and solidifying the droplets in a liquid that does not substantially mix with the liquid mixture.

  In any case of the dropping method, the spraying method, and the stirring method, the temperature of the mixed solution at the time of discharging, spraying, or charging may be set to a temperature not lower than the gelling temperature of the gel forming agent and not higher than 100 ° C. preferable. Further, from the viewpoint that spherical particles having excellent aesthetics can be easily produced, the temperature of the mixed solution is preferably set to the gelation temperature of the gel forming agent + 10 ° C. or higher, and the gelation temperature + 20 ° C. or higher. More preferably. The upper limit of this temperature is 100 ° C., which is the boiling point of water. Here, the dissolution temperature in water of agar often used as a gel forming agent is generally 75 ° C. or higher, and the main one is 75 to 90 ° C. When the agar is dissolved in water and then cooled. The gelation temperature is 30-45 ° C.

  The hydrogel particles thus obtained do not have a film, and the oil gel containing the oil-soluble medicinal component and / or the composite of the water-soluble medicinal component and the water-soluble polymer is gelled. It is dispersed or emulsified in a continuous phase containing a forming agent and water.

  The average particle size of the hydrogel particles in the present invention is preferably 50 to 500 μm, more preferably 100 to 500 μm, and particularly preferably 140 to 290 μm from the viewpoint of delivery to the gingival crevice. The average particle size of the hydrogel particles is expressed as a weight average particle size using various sieves, 100 g of the particles are wet-classified in water, excess water is removed with a filter paper, and the weight is measured (Fluy method). .

  In addition, the shape of the hydrogel particles in the present invention is not particularly limited, but it is preferable to have a shape of a rotating body constituted by a curved surface. Here, the “rotary body constituted by a curved surface” means a closed figure constituted by a virtual axis and a continuous curve, rotated by the virtual axis, and has a shape such as a triangular pyramid or a cylinder. Is not included. The shape of the hydrogel particles is more preferably spherical or elliptical from the viewpoint of aesthetics.

  Furthermore, the hydrogel particles used in the present invention preferably have a breaking strength per particle of 0.1 to 10 g / piece, particularly 1 to 7 g / piece, which is difficult to break during the production of the dentifrice composition, It is preferable because it is delivered to the gingival crevice by brushing and easily broken. This breaking strength is indicated by the amount of load when one hydrogel particle is continuously loaded from above and the hydrogel particle is broken.

[Dental brushing composition]
The dentifrice composition of the present invention contains hydrogel particles as described above, a binder and water.
Examples of the binder used in the present invention include sodium alginate, sodium carboxymethyl cellulose, carrageenan, xanthan gum, sodium polyacrylate, hydroxyethyl cellulose, hydroxypropyl cellulose, pectin, tragacanth gum, gum arabic, guar gum, caraya gum, locust bean gum. , Gellan gum, tamarind gum, psyllium seed gum, polyvinyl alcohol, sodium chondroitin sulfate and methoxyethylene maleic anhydride copolymer, and particularly sodium carboxymethylcellulose, carrageenan and xanthan gum are preferred.

  The binder may be used alone or in combination of two or more. The content of the binder in the dentifrice composition is from the viewpoint of obtaining storage stability, viscosity of the composition, and a higher refreshing feeling. 0.1-3 mass% is preferable, 0.1-2 mass% is more preferable, 0.2-1.2 mass% is still more preferable.

  In the dentifrice composition of the present invention, the content of the hydrogel particles is preferably 0.01 to 15% by mass, more preferably 0.1 to 10% by mass, and 1 to 5% from the viewpoint of the stability of the dentifrice composition. More preferred is mass%.

  The water content in the dentifrice composition of the present invention is preferably 1 to 50% by mass, more preferably 3 to 40% by mass, and even more preferably 5 to 30% by mass from the viewpoint of obtaining storage stability and a higher refreshing feeling. .

The dentifrice composition of the present invention may further contain a powder or particulate erythritol having a particle diameter of less than 355 μm from the viewpoint of a refreshing feeling, a cooling feeling and a taste. As the structure of erythritol, there are three isomers of L-erythritol, D-erythritol, and meso-erythritol, and any of these structures can be used in the present invention. As erythritol, those which are usually available can be used, and examples thereof include crystalline erythritol obtained by recrystallization after fermentation of glucose. As crystalline erythritol, commercially available products such as those manufactured by Nikken Chemical Co., Ltd., Mitsubishi Chemical Foods Co., Ltd., and Celestor are available. Moreover, the thing with a large particle size can use what adjusted the particle diameter by grind | pulverizing. A roller mill, a hammer mill, a high-speed pulverizer, a pulverizer, etc. are generally used to pulverize erythritol, but a high-speed pulverizer and hammer mill that are easy to adjust the particle size and excellent in production efficiency. Is preferred.
The particle diameter of erythritol is preferably 45 μm or more and less than 355 μm, more preferably 53 μm or more and less than 300 μm, and even more preferably 75 μm or more and less than 250 μm, from the viewpoint that the cooling sensation continues in the oral cavity for a long time. Erythritol particles having a particle size of 45 μm or more are preferred because they do not dissolve instantaneously in the mouth and a long cool feeling. Moreover, the thing less than 355 micrometers can melt | dissolve easily in an oral cavity, and can exhibit a cool feeling.

The erythritol particle size is measured as follows.
Sieve: JIS standard sieve φ75mm
Opening: From the upper stage, a receiver is provided under a sieve having openings of 500 μm, 355 μm, 250 μm, 180 μm, 125 μm, 90 μm and 45 μm, respectively.
Shaker: Micro type electromagnetic vibrator M-2 type (Tsutsui Rikenki Co., Ltd.) Method: Place 15 g of sample on a 500 μm sieve, and classify with an electromagnetic vibrator for 5 minutes. The total amount of erythritol present on a sieve having openings of 250 μm, 180 μm, 125 μm, 90 μm and 45 μm is defined as erythritol having a particle size of 45 μm or more and less than 355 μm.

  In the dentifrice composition of the present invention, the blending amount of erythritol is preferably 15 to 60% by mass, more preferably 20 to 55% by mass, and particularly preferably 25 to 50% by mass from the viewpoints of a refreshing feeling and a cool feeling.

  It is desirable that erythritol is dispersed in the dentifrice composition in powder form. For this purpose, erythritol is preferably added as a powder to the final production process. By using such a method, erythritol can be present in a powder state in the dentifrice composition without being substantially dissolved in water.

  The dentifrice composition of the present invention contains other ingredients that can be used in the dentifrice composition, such as foaming agents, abrasives, antioxidants, wetting agents, sweetening agents, flavoring agents, PH adjusting agents, preservatives, etc. You may mix | blend suitably in the range which does not inhibit the objective of this invention.

  Foaming agents include anionic, nonionic, cationic, and amphoteric surfactants. Examples of the anionic surfactant include acyl amino acid salts such as sodium acyl glutamate and acyl sarcosine sodium, alkyl phosphates such as sodium alkyl phosphate, alkyl sulfate salts, higher fatty acid sulfonated monoglyceride salts, fatty acid esters of isethionic acid. Salt, N-methyl long chain acyl taurine sodium salt, polyoxyethylene monoalkyl phosphate and the like. The hydrophobic alkyl group and acyl group in these anionic surfactants preferably have 6 to 18 carbon atoms, particularly 10 to 14 carbon atoms. The salt is preferably a sodium salt. As the anionic surfactant, an alkyl sulfate ester salt is particularly preferable from the viewpoint of good foamability and availability at low cost. It is preferable to contain 0-5 mass% of anionic surfactant in the dentifrice composition of this invention, More preferably, it is 0-2 mass%.

  As abrasives, silica such as precipitated silica, silica gel, aluminosilicate, silconosilicate, gluconosilicate, calcium carbonate, calcium hydrogen phosphate, calcium pyrophosphate, aluminum hydroxide, alumina, magnesium carbonate, magnesium phosphate Etc. 0-15 mass% is preferable in the dentifrice composition of this invention, and, as for content of an abrasive | polishing agent, 0-12 mass% is especially preferable.

  Antioxidants include components that have antioxidant or reducing power and can be used in oral compositions such as L-ascorbic acid and salts thereof, erythorbic acid and salts thereof, rosemary extract, stevia extract, Sunflower seed extract, propyl gallate, dibutylhydroxytoluene, butylhydroxyanisole, L-cysteine hydrochloride, phytic acid, hydroquinone and its glycoside, nordihydroguaiaretic acid, ascorbic acid higher fatty acid ester (lauric acid ester, Stearic acid ester, isostearic acid ester, palmitic acid ester, etc.), guaiac fat and the like. Examples of the salt of L-ascorbic acid or erythorbic acid include sodium salt, calcium salt, ferrous salt, palmitic acid ester salt and the like. These antioxidants may be used alone or in combination of two or more. The content of the antioxidant is 0.0005 to 50% by mass, further 0.001 to 20% by mass, particularly 0.01 to 5% by mass in the dentifrice composition of the present invention, from the viewpoint of the effect of suppressing the change in appearance color. % Is preferred.

  Examples of the wetting agent include glycerin, sorbitol, propylene glycol, 1,3-butylene glycol, xylitol, maltitol, lactitol, trehalose and polyethylene glycol which is also a component of polymer A, polypropylene glycol, and the like. It can mix | blend combining a seed | species or more. The content of these wetting agents is preferably 40 to 95% by mass, more preferably 60 to 80% by mass in the dentifrice composition of the present invention from the viewpoint of ensuring transparency.

  Examples of the sweetener include saccharin sodium, aspartame, thaumatin, acesulfame potassium, stevioside, stevia extract, paramethylicinamic aldehyde, neohesperidyl dihydrochalcone, and perilartin.

  Examples of the flavoring agent include l-menthol, carvone, anethole, eugenol, limonene, peppermint oil, spearmint oil, osimene, n-amyl alcohol, citronellol, α-terpineol, methyl salicylate, methyl acetate, citronoleol acetate, cineol. , Linalool, ethyl linalool, crocodile, thymol, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, pimento oil, perilla oil, clove oil, eucalyptus oil, hatsuka oil, anise oil, winter green oil, etc. It is done.

  Examples of the pH adjuster include citric acid and its salt, phosphoric acid and its salt, malic acid and its salt, gluconic acid and its salt, maleic acid and its salt, aspartic acid and its salt, succinic acid and its salt, Examples include glucuronic acid and its salt, fumaric acid and its salt, glutamic acid and its salt, adipic acid and its salt, hydrochloric acid, alkali metal hydroxide and the like.

  Examples of the preservative include ethyl paraoxybenzoate, methyl paraoxybenzoate, butyl paraoxybenzoate, propyl paraoxybenzoate, sodium benzoate, alkyldiaminoethylglycine hydrochloride, and the like.

  In addition, as other various active ingredients, for example, water-soluble phosphate compounds such as potassium phosphate and sodium salt of orthophosphoric acid; allantochlorohydroxyaluminum, water-soluble glycyrrhetic acid and Anti-inflammatory agents such as salts, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, epidihydrocholesterin, α-bisabolol and its salts; antiplasmin agents such as tranexamic acid and epsilon aminocaproic acid; copper such as copper chlorophyllin sodium and copper gluconate Compounds; salts such as sodium chloride and potassium nitrate; quaternary ammonium compounds such as cetylpyridinium chloride and benzethonium chloride; bactericides such as chlorhexidine salts and trichlorocarbanilide; dextranase, mutanase, amylase, Enzymes such as lysozyme; extracts such as sugarcane, duck, clove, rosemary, ugone, safflower; aluminum lactate, strontium chloride, berberine, hydroxamic acid and its derivatives, sodium tripolyphosphate, zeolite, polyvinylpyrrolidone, zinc citrate, etc. Is mentioned.

  The dentifrice composition of the present invention can be made into a toothpaste composition, a liquid dentifrice composition, a gel-like dentifrice composition or the like according to a conventional method depending on its use.

  In the dentifrice composition of the present invention, the hydrogel particles in the dentifrice composition are delivered to the gingival sulcus by normal brushing operation, i.e., brushing, and are destroyed in the gingival sulcus. Efficiently delivered within. Therefore, the dentifrice composition of the present invention is useful as a dentifrice composition for preventing or improving periodontal disease.

  Unless otherwise specified,% in the examples is% by mass.

Production Example 1
An aqueous solution (85 ° C.) prepared by dissolving 15 g of agar (Ina Food Industry Co., Ltd., UP-37) and 16 g of polyvinylpyrrolidone (ISP, PVP K-90, weight average molecular weight 1300000) in 319 g of ion-exchange water. , 140 g of ion-exchanged water, 10 g of tea extract (Taiyo Kagaku Co., Ltd., Sunphenon 100S, catechin content 60-70%), L-ascorbic acid (Daiichi Pharmaceutical Co., Ltd., ascorbic acid), acrylic acid / methacrylic acid An aqueous solution (20 ° C.) prepared by dissolving an alkyl copolymer (Noveon, Pemlen TR-2), neopentyl glycol dicaprate (Nisshin Oilio Co., Estemol N-01) and triclosan (Ciba Japan (Co., Ltd., Iruga Care MP) is mixed with a homomixer (8000 r / min, 1 minute), An aqueous dispersion of a complex of catechin and polyvinyl pyrrolidone was obtained and sprayed into the gas phase to obtain hydrogel particles a having the composition shown in Table 1. The average particle size of the hydrogel particles a was 200 μm.

Example 1
Dentifrice composition A (invention product) containing hydrogel particles containing triclosan shown in Table 1 and dentifrice composition B (comparative example) containing no hydrogel particles and containing triclosan directly in the dentifrice composition ) Were prepared (Table 2). About the obtained dentifrice composition A and B, the quantity of the triclosan adhering to the gingival crevice model 14 was compared with the following method. In addition, the hydrogel particle a mix | blends the coloring agent in order to confirm the delivery property to the gingival crevice model 14. FIG.

[Evaluation of delivery to gingival crevice]
The delivery property of hydrogel particles and medicinal components to the gingival sulcus was evaluated using the following tooth model 1. As shown in FIG. 1, the tooth model 1 uses a transparent acrylic plate as the tooth model 12, and uses urethane rubber (translucent) similar to the hardness of the gingiva as the gingival model 13.
The urethane rubber of the gingival model 13 is 30 mm in thickness (2 mm) and hardness A (measured with a rubber hardness tester A WR104A from Nishitokyo Seimitsu Co., Ltd., type A durometer in accordance with JIS K 6253). The upper corner portion of R forms a radius of R6 mm. The delivery property was evaluated by setting the lower side where the acrylic plate and the urethane rubber were in close contact with each other than the boundary P between the portion where the upper end of the urethane rubber was rounded and the portion where the urethane rubber and the acrylic plate were in close contact with each other. The urethane rubber used for the gingival model 13 moves slightly by brushing like a human gingiva, and can form a gap of several microns in a portion in close contact with the acrylic plate.

Tooth model 1 was loaded with 1.0 g of dentifrice compositions A and B, brushed for about 1 minute, and then gingival crevice model 14 was rubbed with a cotton swab to contain 5 mL of a moving layer used for the chromatographic method described later. The solution was put into a centrifuge tube, subjected to ultrasonic pouring for 10 minutes, and filtered to obtain a recovered solution. The concentration of triclosan in the recovered liquid was calculated by comparing the recovered liquid with a standard curve using a liquid chromatograph method under the following conditions.
In addition, the delivery ratio of triclosan to the gingival crevice in the recovered liquid is obtained by subjecting the same amount of hydrogel particles as the amount contained in the dentifrice composition used for brushing to ultrasonic extraction with a moving bed for 10 minutes and filtering the solution. The triclosan concentration in the gingival crevice model 14 was calculated assuming that the triclosan concentration in the recovered liquid was 0% although the inside of the gingival crevice model 14 was abraded with a cotton swab before the brushing.

[Conditions for liquid chromatography]
High performance liquid chromatography (HPLC) was applied. The HPLC column uses a stainless steel tube having an inner diameter of 4 to 10 mm and a length of 10 to 30 cm, octadecylsilylated silica gel for liquid chromatography (average particle size of 4 to 10 μm), and an eluent mixture of methanol and water (70: 30) to which phosphoric acid was added to 0.1 w / v% was used at an elution rate of 1.0 mL / min. Triclosan was detected by measuring the absorbance at 254 nm with an ultraviolet absorptiometer. The prepared test solution and 20 μL of the triclosan standard solution were each accurately taken and tested by the above liquid chromatographic method. The peak area of triclosan in each solution was 4000 or more and the tailing coefficient was 0.8. The peak area of the triclosan standard solution was compared as a calibration curve, and the triclosan content in the product was calculated according to the following formula.
Triclosan content in this product = (Y × Z) / X
X: Triclosan peak area obtained by testing the triclosan standard solution Y: Triclosan peak area obtained by testing the test solution Z: Concentration of the triclosan standard solution

<Delivery>
The result is shown in FIG. In the graph of FIG. 2, the average value of the delivery rate of triclosan evaluated five times for each of the dentifrice compositions A and B is shown. As shown in FIG. 2, the dentifrice composition A in which triclosan is blended with hydrogel particles as compared with the dentifrice composition B that does not contain triclosan in the hydrogel particles delivers a medicinal component (triclosan) into the gingival crevicular model 14. The result was about 4 times the amount.

<Visual confirmation>
Next, brushing or the like is performed using the dentifrice composition A in a state where the hydrogel particles enter the gingival sulcus model 14 from the side of the tooth model 12 using a transparent acrylic plate in FIGS. It is shown by the photograph of the state. FIG. 3A shows a state in which the dentifrice composition A is placed and brushed. As can be understood from FIG. 3 (a), the hydrogel particles are delivered to the lower side of the boundary P, about 2 mm, with almost no destruction. This is because the gingival model 13 is slightly moved by brushing, and hydrogel particles are pushed into a gap of several microns formed between the gingival model 13 and the tooth model 12. It is thought that it was sandwiched between and held. FIG.3 (b) is the state which performed massage twice after brushing and washed with water. Since the gingival sulcus model 14 shown in FIG. 3B is transparent or semi-transparent, it was possible to observe a region Q that moved white in the gingival sulcus model 14. Region Q shows a state in which hydrogel particles are destroyed by massage and an oil agent is attached to gingival crevice model 14.

  As described above, the hydrogel particles of the present invention are not easily destroyed by brushing, and the hydrogel particles in an unbroken state enter a slight gap formed between the teeth and gums by brushing. It is thought that it is delivered to the gingival sulcus by being sandwiched and held between them. Furthermore, the delivered hydrogel particles are destroyed so as to be crushed by brushing from the surface side (opposite side of the gingiva), massage, meal, etc., and the medicinal components contained in the hydrogel particles adhere to the gingiva. .

Example 2
In the same manner as in Production Example 1, hydrogel particles c to hydrogel particles h shown in Tables 3 to 8 were produced. Also for the hydrogel particles c to h, a coloring agent was blended in order to confirm the deliverability to the gingival crevice model 14. These hydrogel particles all had an average particle size in the range of 140 to 240 μm. Further, toothpaste compositions C to H shown in Tables 9 and 10 were produced, and brushing was performed using the tooth model 1 shown in FIG. As a result, it was possible to observe that hydrogel particles were delivered to about 2 mm below the boundary P when using any of the dentifrice composition C to the dentifrice composition H.

Claims (4)

(A) Hydrogel particles having an average particle size of 100 to 290 μm, containing medicinal components dispersed or emulsified 0.1 to 15% by mass, (B) binder, and (C) 5 to 40% by mass of water And in component (A),
Oil solubility selected from azulene, tocopherol, glycyrrhetinic acid, triclosan, isopropylmethylphenol, hinokitiol, dihydrocholesterol, and dihydroabietic acid having a content in component (A) of 0.01 to 10% by mass as the medicinal component Medicinal ingredients,
As a solvent for the oil-soluble medicinal component, the content in the component (A) is 0.5 to 10% by mass, and an oil agent selected from isopropyl myristate, isopropyl palmitate, and neopentyl glycol dicaprate,
As a gel forming agent, a method for producing a toothpaste composition for periodontal disease containing agar having a content of 0.5 to 5% by mass in the component (A),
After agar and water are heated and mixed to a temperature higher than the dissolution temperature of the agar, and further mixed with an oil-soluble medicinal component dissolved in an oil agent that is a solvent for the oil-soluble medicinal component, a liquid mixture having a temperature equal to or higher than the dissolution temperature of the agar is obtained. The manufacturing method of the toothpaste composition for periodontal disease including the process of manufacturing the hydrogel particle of a component (A) by cooling from the melting temperature of agar by the dripping method or the spraying method, and solidifying the obtained mixed liquid.   The method for producing a toothpaste composition for periodontal disease according to claim 1, wherein the content of the binder is 0.2 to 2% by mass.   Binder is sodium alginate, sodium carboxymethylcellulose, carrageenan, xanthan gum, sodium polyacrylate, hydroxyethylcellulose, hydroxypropylcellulose, pectin, tragacanth gum, gum arabic, guar gum, caraya gum, locust bean gum, gellan gum, tamarind gum, psyllium seed The method for producing a toothpaste composition for periodontal disease according to claim 1 or 2, which is at least one selected from gum, polyvinyl alcohol, sodium chondroitin sulfate and a methoxyethylene maleic anhydride copolymer.   The manufacturing method of the toothpaste composition for periodontal disease of any one of Claims 1-3 including the process of containing the hydrogel particle manufactured previously.