JP2006069990A - Oral composition - Google Patents

Abstract

An oral composition in which calcium fluoride is efficiently adsorbed on teeth is provided.
A multi-composition system comprising (A) a first composition containing a calcium ion supply compound and (B) a second composition containing a fluorine ion supply compound, and further comprising (C A) malate ion supply compound and (D) a monofluorophosphate ion supply compound. The composition (A), the composition (B), the component (C) and the component (D) are preferably mixed in the oral cavity or immediately before introduction into the oral cavity, and the composition (A) and the composition (B) are mixed. The container is preferably filled in a non-contact state.
[Selection figure] None

Description

  The present invention relates to an oral composition in which calcium fluoride is efficiently adsorbed on teeth.

  Teeth enamel is mainly composed of hydroxyapatite. In the mouth, elution (decalcification) of phosphate ions and calcium ions and crystallization (remineralization) into calcium phosphate and hydroxyapatite are usually in equilibrium. . Fluorine ions suppress decalcification and can prevent the occurrence of caries by promoting the supply and crystallization of calcium ions and phosphate ions, that is, remineralization. Therefore, if fluoride ions and calcium ions are supplied into the oral cavity, remineralization of teeth can be promoted.

  However, if fluorine ions and calcium ions are added to the composition in advance, calcium fluoride is precipitated in the composition. The calcium fluoride produced in advance is in a powder form (average particle size: several μm), and even if it is supplied into the oral cavity, the particle size is too large, so it is hardly adsorbed on the teeth, Tooth remineralization promoting effect is hardly observed.

  From such a viewpoint, the calcium ion source and the fluoride ion source are made into separate compositions, and the two compositions are mixed in the oral cavity or immediately before application to the oral cavity to form calcium fluoride in the oral cavity. An oral preparation has been proposed. For example, there are oral hygiene products (Patent Document 1 and Patent Document 2) containing a calcium ion source, a fluorine ion source, and a calcium metal ion sequestering agent. However, since this oral preparation contains a calcium sequestering agent, there is a problem in that fluorine sequestration on the teeth is inhibited by the sequestering agent.

  Patent Document 3 discloses that calcium fluoride can be rapidly deposited. However, in this case, since the calcium fluoride fine particles (primary particles) after precipitation cannot be controlled in their aggregation rate, self-aggregation proceeds rapidly after the formation of primary particles, and secondary particles are formed. The secondary particles of calcium fluoride formed in this way have a problem that the particle size grows too much and the amount of adsorption onto the teeth decreases.

  Here, the primary particles are crystallites of calcium fluoride formed by fluorine ions and calcium ions. Secondary particles are particles formed by aggregation of the primary particles (for example, self-aggregation).

  Further, Patent Document 2 discloses controlling calcium fluoride formation in glazes, toothpastes and gels. That is, in order to control the formation of calcium fluoride, it has been proposed to incorporate a calcium fluoride inhibitor that delays the precipitation of calcium fluoride for at least about 5 seconds after mixing of calcium and fluoride ions. As a result of blending this calcium fluoride inhibitor, it was possible to achieve a delay in the aggregation of calcium fluoride (formation of secondary particles). However, the presence of the inhibitor was caused by the formation reaction of calcium fluoride (primary particles). The formation of calcium fluoride as primary particles is reduced.

  Therefore, in order to realize more efficient promotion of remineralization, the formation of calcium fluoride (formation of primary particles) is not affected, and the aggregation of calcium fluoride (formation of secondary particles) What could control the speed was desired. As one of the oral compositions in which the aggregation rate of calcium fluoride is controlled, there is an oral composition described in Patent Document 4.

JP 58-219107 A Japanese National Patent Publication No. 10-511956 Japanese Patent Publication No. 6-37382 International Publication No. 2004/060336 Pamphlet

  The object of the present invention is to form more primary particles of calcium fluoride and to control the aggregation rate of calcium fluoride (formation of secondary particles). An object of the present invention is to provide a new composition for oral cavity which is excellent in the effect of suppressing the decalcification of teeth and the effect of promoting remineralization by facilitating the adsorption of calcium fluoride on teeth.

  The inventors of the present invention found that the malate ions made the primary particles of calcium fluoride smaller and further suppressed the aggregation of primary particles (formation of secondary particles), thereby forming secondary particles of calcium fluoride (calcium fluoride). The present invention has been completed by discovering that the particle size of the agglomerates can be controlled.

  That is, the present inventors have (C) a multi-composition system comprising (A) a first composition containing a calcium ion supply compound and (B) a second composition containing a fluorine ion supply compound. By using an oral composition containing a malate ion supply compound and a (D) monofluorophosphate ion supply compound, it was possible to promote the formation of calcium fluoride primary particles and efficiently adsorb it to teeth. .

  If the composition for oral cavity of the present invention is used, by controlling the particle size of calcium fluoride, calcium fluoride can be efficiently adsorbed to the teeth, and the excellent demineralization inhibitory effect and remineralization of teeth can be achieved. A promoting effect is obtained.

  When composite particles containing malate with calcium fluoride are formed as the secondary particles of calcium fluoride, the pH of residual plaque is determined by the pH buffering ability of malate contained in the composite particles. Can be prevented, and as a result, touching can be prevented.

  Furthermore, when calcium fluoride fine particles, monofluorophosphoric acid and malate are present in the secondary particles as composite particles, the synergistic effect of these things suppresses a decrease in pH due to residual plaque, Teeth demineralization is suppressed and remineralization is promoted more effectively, and caries prevention is more effective.

  Examples of calcium ion supplying compounds used in the composition (A) in the present invention include polyol calcium phosphate or sugar phosphate, calcium hydroxide, calcium chloride, calcium acetate, calcium formate, calcium lactate, calcium nitrate, calcium gluconate, calcium benzoate. , Calcium isobutyrate, calcium propionate, calcium salicylate, calcium carbonate, calcium hydrogen phosphate, calcium phosphate, hydroxyapatite and mixtures thereof. Examples of the polyol calcium phosphate or sugar calcium phosphate include calcium glycerophosphate, glucose-1-calcium phosphate, glucose-6-calcium phosphate, and the like. From the viewpoint of good taste, preferred calcium ion supply compounds include calcium lactate and calcium glycerophosphate.

  The calcium ion supply compound in the composition (A) has a calcium ion content of 10 to 16000 ppm, more preferably 50 to 12000 ppm in the composition (A) from the viewpoint of efficiently producing calcium fluoride in the oral cavity. It is particularly preferable to supply 200 to 8000 ppm. As the calcium ion supply compound according to the present invention, it is preferable to use an ionized calcium ion supply compound. When the amount of the composition (A) and the composition (B) used is the same amount (in terms of mass), these calcium ion supply compounds are added in the composition (A) at 0.25 to 400 μmol / g, and further 1.25 It is preferable to contain ˜300 μmol / g, particularly 5 to 200 μmol / g.

  In the present invention, the fluorine ion supply compound used in the composition (B) is a fluorine supply compound other than the compound that supplies monofluorophosphate ions, such as sodium fluoride, stannous fluoride, and potassium fluoride. Zinc fluoride, betaine fluoride, stannous alanine fluoride, sodium fluorosilicate, hexyl fluoride, and mixtures thereof. A preferred fluoride ion supplying compound is sodium fluoride or stannous fluoride.

  The fluorine ion supplying compound in the composition (B) has a fluorine ion content of 5 to 4000 ppm, more preferably 25 to 2000 ppm, particularly 100 in the composition (B) from the viewpoint of efficiently producing calcium fluoride in the oral cavity. It is preferable to supply ~ 1000 ppm. In order to make the fluorine ion concentration within this range, for example, when the amounts used of the compositions (A) and (B) are the same amount (in terms of mass), these in the composition (B) It is preferable to contain 0.065 to 210 μmol / g of a fluorine ion supply compound, more preferably 0.325 to 158 μmol / g, and particularly preferably 2.6 to 105 μmol / g.

  Calcium ions and fluoride ions react at 1: 2 (molar ratio) to produce calcium fluoride. The content ratio (molar ratio) between the calcium ion supply compound (calcium conversion) and the fluorine ion supply compound (fluorine conversion) in the oral composition of the present invention is 1: 8-4: 1 are preferable, and 1: 4-2: 1 are particularly preferable.

  The malate ion supply compound used as component (C) in the present invention is malic acid and / or a salt thereof, and examples thereof include malic acid, sodium malate, and potassium malate. The content of the composition (A) and the composition (B) is the same amount (in terms of mass), and the component (D) is contained only in the composition (A). In (A), 0.02-20 mass% is preferable, More preferably, it is 0.1-10 mass%. Within this range, aggregation due to micronization, remineralization promotion, and calcium fluoride formation promotion occur.

  The malate ion supply compound as component (C) may be contained in one or both of the composition (A) and the composition (B), or the composition (A) and the composition ( It may be present separately from B) as a third component or as one component contained in a third composition.

  Examples of the monofluorophosphate ion supply compound used for the component (D) in the present invention include sodium monofluorophosphate, potassium monofluorophosphate, magnesium monofluorophosphate, calcium monofluorophosphate, and the like. Sodium acid is preferred. Monofluorophosphate ions remain in the oral cavity, especially in plaque, and are gradually decomposed by phosphatase in saliva and plaque, and continuously supply fluoride ions to the teeth. The content of monofluorophosphate ion is the same amount (in terms of mass) of the composition (A) and the composition (B) used, and the component (D) is contained only in the composition (A). Is preferably 0.065 to 210 μmol / g, more preferably 0.325 to 158 μmol / g, and particularly preferably 2.6 to 105 μmol / g in the composition (A).

  The monofluorophosphate ion supply compound as component (D) may be contained in one or both of the composition (A) and the composition (B), or the composition (A) and the composition. It may be present separately from the product (B) as a third component or as one component contained in the third composition.

  In the composition for oral cavity of the present invention, the composition (A), the composition (B), the component (C), and the component (D) are preferably mixed in the oral cavity or immediately before introduction into the oral cavity. Furthermore, in the composition for oral cavity of the present invention, it is preferable that the composition (A) and the composition (B) are filled in a container in a non-contact state and mixed in the oral cavity or immediately before introduction into the oral cavity.

In the present invention, it is preferable that the composition (A) and the composition (B) are stored in a non-contact state at the time of use or immediately before use, and take the form of a multi-composition system. In order to achieve the above, the composition (A) and the composition (B) may be filled in separate containers, and the composition (A) and the composition (B) are in a non-contact state in one container. It may be filled. As a container for filling in a non-contact state, for example, a tube provided with a partition, a tube inserted into the tube, a tube joined with separate tubes joined together at the mouth, etc. It is done.

  Examples of the combination of the composition and the component in the multi-composition system of the present invention include the following combinations.

<Two composition system>
(1) Combination of composition (A) and composition (B) in which components (C) and (D) are blended (2) Composition in which composition (A) and components (C) and (D) are blended Combination of product (B) (3) Composition (A) containing component (C) and composition (B) containing component (D) (4) Composition containing component (D) Combination of composition (B) in which product (A) and component (C) are mixed

<Three composition system>
(5) Composition (A) containing component (D), combination of composition containing composition (B) and component (C) (6) Composition containing component (C) (A ), Composition (B) and component (D) in combination (7) composition (A) and component (D) in composition (B) and component (C) in combination (8) Combination of composition (A) and pre-composition (B) containing component (C) and composition (B) containing component (D)

<Four composition system>
(9) Combination of composition (A), composition (B), composition containing component (C) and composition containing component (D) Composition (A), Composition (B), When the component (C) and the component (D) are mixed, calcium fluoride is generated. The primary particles are preferably fine particles, that is, an average particle size of 0.3 to 15 nm, more preferably 0.3. It is -12 nm, Most preferably, it is 0.3 nm-9 nm.

  The secondary particles that are aggregates of fine particle calcium fluoride may contain monofluorophosphoric acid, and the content of monofluorophosphoric acid in the aggregate is preferably 0.05 to 20% by mass, more Preferably, the content is 0.1 to 15% by mass, and particularly preferably, the content is 0.5 to 10% by mass. The secondary particles of fine calcium fluoride can also contain malate, and the content of malate in the aggregate is preferably 0.05 to 20% by mass, more preferably, Content is 0.1-15 mass%, Most preferably, it is 0.5-10 mass%. Furthermore, monofluorophosphoric acid and malate may be contained simultaneously, and the composite particle of monofluorophosphoric acid and malate may be sufficient. The total content of monofluorophosphates and malates in the composite particles is preferably 0.1 to 40% by mass, more preferably the total content is 0.2 to 30% by mass, and particularly preferably 1 to 20%. % By mass.

The oral composition of the present invention preferably contains 10 to 70% by mass of sugar alcohol as a concentration in the mixture immediately before use. Here, examples of the sugar alcohol include lactitol, isomaltitol, maltotriitol, isomaltitol, panitol, isomaltotetriitol, erythritol, arabitol, ribitol, xylitol, sorbitol, mannitol, maltitol, and the like. It is done. Such sugar alcohol may be either D-form or L-form, or a mixture thereof. In addition, these sugar alcohols preferably contain xylitol, and the xylitol concentration in the sugar alcohol Is preferably 1 to 40% by mass, more preferably 2 to 20% by mass.

  In the present invention, an anionic surfactant generally used in an oral composition, for example, an alkyl sulfate ester salt such as sodium lauryl sulfate, an N-acyl amino acid salt such as N-acyl sarcosinate salt, and the like may be contained. . Also commonly used in oral compositions, abrasives such as silicic anhydride, calcium hydrogen phosphate, calcium carbonate, wetting agents such as glycerin and polyethylene glycol, foaming agents, sodium carboxymethylcellulose, carrageenan, etc. Binders, sweeteners such as saccharin sodium, coloring agents, preservatives such as methyl paraoxybenzoate, bactericides such as benzethonium chloride, triclosan, isopropylmethylphenol, anti-inflammatory agents such as β-glycyrrhetinic acid, tocopherol, and fragrances Can be added. These components may be blended in both the composition (A) and the composition (B), or may be blended in either one.

  When the composition for oral cavity according to the present invention is used, more primary particles of calcium fluoride can be formed, while the aggregation rate of calcium fluoride (formation of secondary particles) can be controlled. As a result, more particulate calcium fluoride can be easily adsorbed to teeth, etc., and it has excellent adsorptivity to the tooth surface in the oral cavity, preventing demineralization of teeth and promoting remineralization of teeth. An oral composition having an excellent effect can be obtained.

  Further, when the composition for oral cavity according to the present invention containing malate is used, the secondary particles of calcium fluoride become composite particles when calcium fluoride secondary particles are formed. Can be present. Due to the pH buffering ability of malate contained in the composite particles, it acts to suppress the decrease in pH of residual plaque (particularly residual plaque after brushing), and as a result, the pH of plaque is decreased. It is possible to prevent dental caries due to the above. In addition, when the secondary particles are composite particles of calcium fluoride fine particles and monofluorophosphoric acids, the effect of improving the decalcification of teeth by monofluorophosphoric acids, The effect of promoting remineralization is enhanced, and these effects also prevent dental caries.

  The composition for oral cavity of this invention can be used as a powder dentifrice, a moisturizing dentifrice, a toothpaste, a liquid dentifrice, a mouthwash, etc.

A. Mouthwash 1. Preparation of Mouthwash Liquid According to the composition of Table 1, two preparations, composition (A) and composition (B), were prepared, respectively, and filled in equal amounts of isolated containers.

2. Measuring method a. Quantification of Fluorine Adsorption onto Hydroxyapatite (HAP) Pellets HAP pellets are each treated with 10 ml of Composition A for 30 seconds and then with 10 ml of Composition B for 30 seconds. This treatment was carried out alternately for 3 minutes. By such treatment, calcium fluoride fine particles adsorbed on the HAP pellet surface are extracted with hydrochloric acid, and fluorine adsorbed on the HAP pellet surface is extracted with an ion analyzer (Expandable) using a fluorine ion electrode (inplus-Fluoride (ORION)). Quantification was performed using ion Analyzer EA940 (ORION).

b. Measurement of Size of Calcium Fluoride Primary Particles HAP powder and HAP powder samples treated with the compositions of Example 1 and Comparative Example 1 shown in Table 1 were analyzed by powder X-ray diffraction (apparatus: Rigaku Electric RINT2500VPC, Cu: Kα, 40kV, 120mA, divergence slit 1 °, divergence length limit slit 10mm, scattering slit 1.25mm, light receiving slit 0.3mm, scan speed 1.000 ° / min), 2θ 2.5-75 °
It measured in the range of.

c. Component analysis of secondary particles of calcium fluoride Identification and quantification of each agent in the HAP powder sample treated with the composition of Example 1 were performed by ion chromatography. For sample preparation, 0.1 g of a HAP powder sample was precisely weighed in a beaker, 40 ml of ultrapure water was added, 0.5 ml of 0.01 mol / l-HCl was added, and the mixture was stirred for 1 hour. The slurry was filtered through a membrane filter having a diameter of 45 μm, the first 5 ml was discarded, and the subsequent solution was used as an ion chromatograph measurement solution. Ion chromatographic measurement is performed by using DX-320 (equipped with EG-40) manufactured by Dionex, identified by comparing retention times with monofluorophosphoric acid and malic acid standard substances, and quantified from the peak area using a calibration curve method. Went.

  The quantitative conditions for monofluorophosphoric acid and malic acid are as follows: separation column IonPacAS-16, guard column IonPacAG-16, eluent KOH (using EG-40 Eluent generator), flow rate 1.0 ml / min, gradient 10 mmol / l-70 mmol / l (0-25 min), suppressor ASRS-ULTRA 4 mm (200 mA), and the detector was an electric conductivity detector.

3. Results a. Fluorine adsorption amount and adsorption state on HAP pellets As shown in Table 1, alternating composition A composed of malic acid, calcium lactate and sodium monofluorophosphate of Example 1 and composition B containing sodium fluoride The fluorine adsorption amount on the treated HAP pellet was 1.25 μg / cm ² .

That is, in the case of Example 1, the presence of malic acid suppresses the formation of calcium fluoride fine particles (primary particles) formed by sodium monofluorophosphate into secondary particles, and as a result, the state of primary particles Thus, the amount of fluorine adsorbed on the HAP pellet was 1.25 μg / cm ² .

Moreover, when the composition A of Example 2 is calcium lactate and sodium monofluorophosphate, and B is malic acid and sodium fluoride, the amount of fluorine adsorbed on the HAP pellets by the alternating treatment of the composition A and the composition B is It was 1.46 μg / cm ² .

On the other hand, when the A agent of Comparative Example 1 is calcium lactate and sodium monofluorophosphate, and the composition B is sodium fluoride, the amount of fluorine adsorbed on the HAP pellets by the alternating treatment of the composition A and the composition B is It was 0.69 μg / cm ² . It is clear that the amount of adsorption decreases when malic acid is not contained.

In the case where the composition A containing sodium monofluorophosphate of Comparative Example 2 and the composition B containing sodium fluoride were alternately treated, calcium fluoride was not formed because it did not contain calcium, and the fluorine adsorption amount was 0.14. It was μg / cm ² .
Further, when the composition A containing malic acid and sodium monofluorophosphate and the composition B containing sodium fluoride were alternately treated as in Comparative Example 3, the fluorine adsorption amount was 0.12 μg / cm ^2. The results were as low as in Example 2.

b. Analysis of primary particle (crystallite) diameter of calcium fluoride by X-ray diffraction
The presence of CaF ₂ was confirmed at the diffraction peaks of CaF ₂ (PDF No. 35-0816) at d = 3.1546 (111), d = 2.7314 (200), and d = 1.9316 (220). Focusing on the d = 3.1546 (111) part of CaF ₂ that is most easily separated without overlapping with the hydroxyapatite peak, the diffraction peaks of various treated HAP powders and untreated HAP powders (control group) In the range of 2θ = 26.0 ° to 31.0 °, the peak of CaF ₂ alone was separated by taking the difference. The crystallite size (Å) was calculated by the Scherrer equation (D = Kλ / (B · cosθ)) using the diffraction angle and half-width (width at half the peak height) of the separated peak (CaF ₂ ). . Here, coefficient K = 0.9, CuKαλ = 1.54056Å, B: peak half width (width (rad) at half of peak height), θ: diffraction angle (peak top position).

  As a result, the crystallite size (particle diameter) of Examples 1 and 2 was 5 nm and 4 nm. The crystallite size of Comparative Example 1 was 7 nm, and Comparative Examples 2 and 3 could not be measured because the amount of fluorine uptake was small.

e. Component analysis of secondary particles of calcium fluoride The quantitative value by ion chromatography of Example 1 is 0.5% by mass for malic acid, 1.1% by mass for monofluorophosphoric acid, Example 2 is 0.6% by mass for malic acid, and monofluoro Phosphoric acid was 1.4% by mass. In Comparative Examples 2 and 3, the amount of malic acid or monofluorophosphoric acid adsorbed was below the limit of quantification.

B. Dentifrice 1. Preparation of dentifrice According to the composition of Table 2, two preparations were prepared and filled in equal amounts each in a dentifrice container having a partition in the tube.

２．測定方法
ＨＡＰペレットへのフッ素吸着量の定量
ＨＡＰペレットを、２倍希釈した１０ｍｌの組成物Ａで３０秒間処理し、次に２倍希釈した１０ｍｌの組成物Ｂで３０秒間処理する。この処理を交互に３分間行った。このような処理によって、ＨＡＰペレット表面に吸着したフッ化カルシウム微粒子を塩酸で抽出し、ＨＡＰペレット表面に吸着したフッ素を、フッ素イオン電極（ionplus-Fluoride(ORION社製)を用い、イオンアナライザー(Expandable ion Analyzer EA940(ORION社製))を使用して、定量した。

2. Measurement Method Quantification of Fluorine Adsorption onto HAP Pellets HAP pellets are treated with 10 ml of Composition A diluted 2 times for 30 seconds and then treated with 10 ml of Composition B diluted 2 times for 30 seconds. This treatment was carried out alternately for 3 minutes. By such treatment, calcium fluoride fine particles adsorbed on the surface of the HAP pellet are extracted with hydrochloric acid, and fluorine adsorbed on the surface of the HAP pellet is extracted with an ion analyzer (Expandable) using a fluorine ion electrode (ionplus-Fluoride (ORION)). Quantification was performed using ion Analyzer EA940 (ORION).

3. Results As shown in Table 2, the amount of fluorine adsorbed on the alternately processed HAP pellets of the composition A composed of malic acid, calcium lactate and sodium monofluorophosphate of Example 3 and the composition B containing sodium fluoride. Was 1.12 mg / cm ² . Further, when the composition A of Example 4 is calcium lactate and sodium monofluorophosphate, and B is malic acid and sodium fluoride, the amount of fluorine adsorbed on the HAP pellets by the alternate treatment of the composition A and the composition B Was 1.35 μg / cm ² .

Comparative Example 4 is fluorine adsorption 0.58μg / cm ^2, Comparative Example 5 0.11μg / cm ^2, Comparative Example 6 none of the comparative examples and 0.12μg / cm ^2, fluorine uptake was low.

Claims (6)

A multi-composition system comprising the following composition (A) and composition (B), wherein the multi-composition system further comprises the following components (C) and (D): .
(A) First composition containing calcium ion supply compound (B) Second composition containing fluorine ion supply compound (C) Malate ion supply compound (D) Monofluorophosphate ion supply compound   The composition for oral cavity according to claim 1, wherein the composition (A), the composition (B), the component (C) and the component (D) are mixed in the oral cavity or immediately before introduction into the oral cavity.   The composition for oral cavity according to claim 2, wherein when the composition (A), the composition (B), the component (C) and the component (D) are mixed, particulate calcium fluoride is produced.   The composition for oral cavity according to claim 3, wherein the fine particle calcium fluoride forms secondary particles, and the secondary particles contain monofluorophosphoric acids and / or malic acid.   The composition for oral cavity according to claim 4, wherein the content of monofluorophosphoric acids in the secondary particles is 0.05 to 20% by mass, and the content of malic acid is 0.05 to 20% by mass. The composition for oral cavity according to any one of claims 1 to 5, wherein the composition (A) and the composition (B) are filled in a container in a non-contact state.