CN117529302A - Dentifrice composition - Google Patents

Abstract

Provided is a dentifrice composition which is excellent in the retention of fluoride ions in the oral cavity, particularly in the oral mucosa, and has excellent release properties, and has liquid separation stability, solidification stability, and good storage stability. A dentifrice composition containing: (A) water-soluble polyphosphate, (B) glycerol calcium phosphate, (C) water-soluble fluorine-containing compound, and (D) cationized cellulose.

Description

Dentifrice composition

Technical Field

The present invention relates to a dentifrice composition containing a water-soluble fluorine-containing compound, which has excellent retention of fluorine ions in the oral cavity, particularly in the oral mucosa, and also has excellent release properties.

Background

For the purpose of preventing dental caries, fluorine-containing compounds such as sodium fluoride are widely used in oral compositions such as dentifrice compositions as pharmaceutical ingredients having functions of promoting remineralization, suppressing demineralization, and the like. In order to effectively act a fluorine-containing compound, it is effective to retain fluorine ions on the tooth surface in the oral cavity for a long period of time, and it is important that a large amount of fluorine ions remain in the oral cavity even after rinsing the mouth after use and rinsing the oral cavity with water, but particularly, a dentifrice composition is rinsed off at the time of rinsing after tooth brushing, and therefore, the amount of fluorine ions remaining in the oral cavity is only a minute amount.

In order to improve the retention of fluoride ions in the oral cavity blended in the dentifrice composition, there is a method of allowing calcium ions and fluoride ions as remineralizing components to coexist, but the calcium ions and fluoride ions have high reactivity, and calcium fluoride as an insoluble substance is formed before acting on teeth in the coexistence, so that a sufficient effect cannot be exerted. In addition, patent document 1 (japanese patent application laid-open No. 10-511956) proposes an oral preparation in which calcium fluoride is produced in the oral cavity by mixing calcium ions and fluorine ions in the oral cavity with these 2 compositions or mixing these 2 compositions immediately before application to the oral cavity. However, in this method, fluorine ions are taken into the oral cavity and immediately carried away by saliva, whereby a sufficient retention effect cannot be exhibited, and further, calcium fluoride is precipitated in a short period of time after mixing of 2 components, whereby fluorine ions are not sufficiently released, and a remineralization preventing effect cannot be satisfactorily exhibited. Patent document 2 (japanese patent application laid-open No. 2009-137863) proposes a composition obtained by preparing a complex of polyphosphate, calcium salt, and fluoride salt in advance, but this method has problems such as complicated preparation, fluidization and solidification after long-term storage as a dental cleaning agent.

Patent documents 3 to 5 (japanese patent application laid-open publication No. 2015-117215, japanese patent application laid-open publication No. 2013-67567, and japanese patent application laid-open publication No. 2007-320894) propose a method of adsorbing and retaining fluorine ions on the tooth surface by using a specific cationic polymer in a dentifrice composition, but there is still room for improvement in retention and residual amount after brushing, and further improvement in retention is desired.

Prior art literature

Patent literature

Patent document 1: japanese patent Kokai publication Hei-10-511956

Patent document 2: japanese patent laid-open No. 2009-137863

Patent document 3: japanese patent application laid-open No. 2015-117215

Patent document 4: japanese patent laid-open No. 2013-67567

Patent document 5: japanese patent laid-open No. 2007-320894

Disclosure of Invention

Problems to be solved by the invention

The present invention has been made in view of the above circumstances, and an object thereof is to provide a dentifrice composition excellent in retention of fluoride ions in the oral cavity, particularly in the oral mucosa, and also excellent in release.

Solution for solving the problem

The present inventors have conducted intensive studies to achieve the above object and as a result, found that: when a water-soluble polyphosphate and calcium glycerophosphate are used in combination with a water-soluble fluorine-containing compound, and a cationized cellulose is further combined and blended into a dentifrice composition, the composition is excellent in retention of fluorine ions in the oral cavity, particularly in the oral mucosa, and the composition is excellent in release of fluorine ions (release amount, release property) and can provide fluorine ions in the oral cavity for a long period of time, and can inhibit separation and solidification of a liquid after long-term storage, thereby achieving good storage stability. That is, the present invention has been completed by finding that in a dentifrice composition containing (a) a water-soluble polyphosphate, (B) calcium glycerophosphate, (C) a water-soluble fluorine-containing compound and (D) a cationized cellulose, the retention of fluorine ions in the oral cavity, particularly in the oral mucosa, is excellent, the release properties thereof are also excellent, and further, the composition has liquid separation stability and solidification stability and also good storage stability.

If fluorine of the water-soluble fluorine-containing compound blended in the dentifrice composition is sufficiently retained not only on the tooth surface but also on the oral mucosa, further improvement in the retention in the oral cavity can be expected, but since the oral mucosa is covered with a salivary protein such as mucin, fluorine is difficult to adsorb, and the conventional art cannot sufficiently retain fluorine on the oral mucosa. In the present invention, by using the component (a) and the component (B) in combination and the component (D) in combination, the retention of fluorine ions derived from the component (C) to the oral mucosa can be improved, and not only the retention of fluorine ions but also the release thereof can be excellent. In this case, the component (D) improves the adsorption of fluorine ions to mucin covering the oral mucosa, so that the retention property is improved, fluorine ions are retained in the oral mucosa at a high rate, and the retained fluorine ions are gradually released into saliva and supplied to the tooth surface in contact with the saliva for a long period of time. Thus, according to the dentifrice composition of the present invention, liquid separation stability and solidification stability can be ensured to improve the intraoral retention of fluoride ions.

As shown in comparative examples described below, when the (a), (B) and (C) components are blended but the (D) component is not blended, the fluorine (fluoride ion) retention and fluorine (fluoride ion) release properties are poor, the liquid separation stability of the preparation is poor (comparative example 3), and when the (D) component is blended but the (a) or (B) component is not blended, the fluorine retention and fluorine release properties are poor, and the liquid separation stability of the preparation or the solidification stability of the preparation is poor (comparative examples 1 and 2). In contrast, the dentifrice composition containing components (a), (B), (C) and (D) of the present invention (examples described below) is excellent in fluorine retention and fluorine release, and the liquid separation stability and solidification stability of the formulation are good.

Accordingly, the present invention provides the following dentifrice compositions.

〔1〕

A dentifrice composition comprising:

(A) A water-soluble polyphosphate,

(B) Calcium glycerophosphate,

(C) Water-soluble fluorine-containing compound

And

(D) Cationized cellulose.

〔2〕

The dentifrice composition according to [ 1], wherein the component (A) is potassium pyrophosphate.

〔3〕

The dentifrice composition according to [ 1] or [ 2], wherein the molar ratio of (A)/(C) is 0.05 to 1.

〔4〕

The dentifrice composition according to any one of [ 1] to [ 3], wherein (B)/(C) is 0.05 to 1.5 in terms of a molar ratio.

〔5〕

The dentifrice composition according to any one of [ 1] to [ 4], wherein the content of the component (A) is 0.1 to 1.5% by mass, the content of the component (B) is 0.1 to 2% by mass, the content of the component (C) is 500 to 5,000ppm in terms of fluorine ion, and the content of the component (D) is 0.01 to 0.5% by mass.

〔6〕

The dentifrice composition according to any one of [ 1] to [ 5], which is a paste dentifrice or gel dentifrice.

ADVANTAGEOUS EFFECTS OF INVENTION

According to the present invention, it is possible to provide a dentifrice composition which is excellent in retention of fluoride ions in the oral cavity, particularly in the oral mucosa, is excellent in release properties, has liquid separation stability and solidification stability, and is excellent in storage stability. The dentifrice composition of the present invention can retain a large amount of fluoride ions in the oral cavity even after rinsing the oral cavity with water after brushing teeth, and can sufficiently exhibit the effects of promoting remineralization and inhibiting demineralization of water-soluble fluorochemicals, and is suitable for use in preventing dental caries.

Detailed Description

The present invention will be described in more detail below.

The dentifrice composition of the present invention comprises: (A) a water-soluble polyphosphate, (B) calcium glycerophosphate, (C) a water-soluble fluorine-containing compound, and (D) a cationized cellulose.

(A) The water-soluble polyphosphate plays a role in improving the retention of fluoride ions and also plays a role in inhibiting liquid separation.

As the component (a), water-soluble polyphosphates may be mentioned: linear polyphosphoric acids such as pyrophosphoric acid, tripolyphosphoric acid and tetraphosphoric acid; examples of the salts of cyclic polyphosphoric acids such as trimetaphosphate, tetrametaphosphoric acid and hexametaphosphoric acid include: alkali metal salts such as sodium salts and potassium salts. Among these, pyrophosphate and tripolyphosphate are preferable, pyrophosphate is more preferable, and potassium pyrophosphate is particularly preferable. These may be used alone or in combination of 1 or more than 2.

(A) The blending amount of the components is preferably 0.1 to 1.5% by mass (hereinafter, the same applies), more preferably 0.15 to 1.4%, still more preferably 0.3 to 1.0% by mass of the entire composition. When the amount is 0.1% or more, the retention and release properties of fluorine ions can be sufficiently obtained, and further, liquid separation can be suppressed even with time, and sufficient liquid separation stability can be obtained. When the concentration is 1.5% or less, the retention and release properties of fluorine ions are sufficiently maintained, and further, curing with time can be prevented, whereby sufficient curing stability can be obtained.

(B) The calcium glycerophosphate plays a role in improving the retention of fluoride ions and also plays a role in inhibiting solidification.

The calcium glycerophosphate may be derived from natural sources or may be synthesized. For example, a commercially available product such as "calcium glycerophosphate" manufactured by Kagaku Co., ltd may be used.

(B) The amount of calcium glycerophosphate to be blended is preferably 0.1 to 2%, more preferably 0.15 to 1.8%, particularly preferably 0.25 to 1.5% of the entire composition. When the amount is 0.1% or more, the retention and release properties of fluorine ions can be sufficiently obtained, and further, curing with time can be prevented, and sufficient curing stability can be obtained. When the concentration is 2% or less, the retention and release properties of fluoride ions are sufficiently maintained, and further, the liquid separation with time is suppressed, whereby sufficient liquid separation stability can be obtained.

The water-soluble fluorine-containing compound (C) includes: sodium fluoride, sodium monofluorophosphate, tin fluoride, and the like.

(C) The amount of the water-soluble fluorine-containing compound to be blended is preferably 500 to 5,000ppm, more preferably 1,100 to 3,000ppm, of the entire composition in terms of fluorine ion. When the amount of the fluorine ion is 500ppm or more, the effect of improving the retention of fluorine ions can be sufficiently obtained, and when the amount is 5,000ppm or less, the occurrence of a harmful effect such as plaque and teeth due to excessive ingestion can be prevented.

The amount of the water-soluble fluorine-containing compound to be blended varies depending on the amount of the supplied fluorine ion, and for example, in the case of sodium fluoride, the amount of the fluorine ion to be blended is 0.11% of the total composition when the amount of the supplied fluorine ion is 500 ppm. Specifically, the blending amount of sodium fluoride is preferably 0.1% or more, more preferably 0.25 to 0.7% of the entire composition.

In the present invention, the molar ratio of (A)/(C), which represents the ratio of the amount of the component (A) to the amount of the component (C), is preferably 0.05 to 1, more preferably 0.1 to 0.5, and particularly preferably 0.10 to 0.50. The molar ratio of (B)/(C), which represents the ratio of the amount of the component (B) to the amount of the component (C), is preferably 0.05 to 1.5, more preferably 0.10 to 1. The molar ratio of (A)/(C) and the molar ratio of (B)/(C) are each in the above-mentioned range, more preferably. When the component (C) is blended in the range of these molar ratios, the retention and release properties of fluorine ions are more excellent, and the liquid separation stability and the solidification stability are more excellent.

(D) The cationized cellulose, in combination with the components (a) and (B), has an effect of improving retention of fluorine ions derived from the component (C) and improving release thereof, and has an effect of improving liquid separation stability.

The cationized cellulose is cellulose having a cation or a cellulose derivative having a cation. The cationized cellulose may have a counter ion (e.g., a halide (chloride), methyl sulfate, etc.). The molecular weight of the cationized cellulose is not particularly limited. As the component (D), 1 kind of cationized cellulose may be used alone or 2 or more kinds may be used in combination.

Examples of the cationized cellulose include: the hydroxyethylcellulose dimethyldiallylammonium salt and O- [ 2-hydroxy-3- (trimethylamino) propyl ] hydroxyethylcellulose chloride are preferably hydroxyethylcellulose dimethyldiallylammonium salts.

As the counter ion, a chloride ion is exemplified for hydroxyethylcellulose dimethyl diallyl ammonium salt, and hydroxyethylcellulose dimethyl diallyl ammonium chloride is preferable.

The cationized cellulose used in the present invention preferably has a 2% aqueous solution viscosity (BH-type Brookfield viscometer, rotor No.2, 20 rpm, 20 ℃ C., measurement time of 1 minute) of 30 to 3,000 mPas.

The average molecular weight of the cationized cellulose is not particularly limited, and a weight average molecular weight of 100,000 ～ 1,500,000 obtained by a Gel Permeation Chromatography (GPC) method using polyethylene glycol as a standard substance is preferable. The nitrogen content is preferably 0.1 to 3%, more preferably 0.5 to 2.5%.

Examples of such cationized cellulose include and use of: CELQUAT L-200 (viscosity of 2% aqueous solution: 35 to 350 mPas, BH-type Brookfield viscometer, rotor No.2, 20 rpm, 20 ℃ C., measurement time: 1 minute) sold by Akzo Nobel Co., ltd.) and a weight average molecular weight obtained by Gel Permeation Chromatography (GPC) method using polyethylene glycol as a standard substance: 250,000 ～ 350,000).

(D) The blending amount of the components is preferably 0.01 to 0.5%, more preferably 0.05 to 0.2% of the entire composition. When the amount of the fluorine ion is 0.01% or more, retention and release of fluorine ions can be sufficiently obtained, and further, liquid separation can be suppressed even with time, and sufficient liquid separation stability can be obtained. When the content is 0.5% or less, the uncomfortable feeling to the oral mucosa can be sufficiently suppressed.

The ratio of the amount of the component (A)/(D) to the amount of the component (D) is preferably 1 to 50, more preferably 3 to 25.

The ratio of (B)/(D) representing the amount of the component (B) to the component (D) is preferably 1 to 50, more preferably 2 to 30, in terms of mass ratio.

The ratio of the amount of the component (C)/(D) to the amount of the component (D) is preferably 1 to 20, more preferably 1 to 10.

When the component (D) is blended in the range of these mass ratios, the effect of the component (D) can be fully exerted, the retention of fluorine ions and the release thereof are more excellent, and the liquid separation stability is more excellent.

The dentifrice composition of the present invention is particularly suitable as a paste-like dentifrice or gel-like dentifrice (without adding an abrasive), and in particular, a paste-like dentifrice, and other known ingredients may be added as required in addition to the above-described ingredients within a range that does not impair the effects of the present invention. For example, an abrasive, a binder, a thickener, a surfactant, and optionally a coloring agent, a sweetener, a preservative, a flavor, an active ingredient, and the like can be blended. The method for producing the dentifrice composition is not particularly limited, and may be any known method according to the dosage form, and for example, the dentifrice composition may be produced by mixing the components (a) to (D), and further any components, and water by a usual method.

Examples of the polishing agent include: silica-based abrasives such as anhydrous silicic acid, precipitated silica, silica gel, aluminosilicate, and zirconium silicate; calcium phosphate monobasic dihydrate or anhydrate; calcium phosphate compounds such as monocalcium phosphate, calcium phosphate, tetracalcium phosphate, and calcium pyrophosphate; calcium carbonate, calcium hydroxide, aluminum hydroxide, insoluble sodium metaphosphate, magnesium phosphate, magnesium carbonate, calcium sulfate, bentonite, titanium-bonded silicate and synthetic resin abrasive. Among them, silica-based abrasives are preferable.

The amount of the polishing agent to be blended is preferably 5 to 60%, particularly preferably 5 to 30% of the entire composition.

The binder may be blended with an organic or inorganic binder. Specifically, there may be mentioned: cellulose derivatives such as sodium carboxymethyl cellulose, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, and hydroxymethyl ethyl cellulose; alginic acid derivatives such as sodium alginate; gums such as xanthan gum, tragacanth gum, karaya gum, and gum arabic; organic binders such as polyacrylates, carrageenans, polyvinyl alcohol, carboxyvinyl polymers, and the like; inorganic binders such as thickening silica, thickening aluminum silica, and VEEGUM, LAPONITE.

The amount of the binder to be blended is preferably 0.1 to 5%, particularly preferably 0.2 to 3% of the entire composition. In the present invention, the organic binder is particularly preferable, and the amount of the organic binder is preferably 0.1 to 5%, particularly preferably 0.5 to 3%, of the total composition. The inorganic binder, particularly the thickening silica, is preferably 5% or less, particularly preferably 2% or less, particularly preferably 1% or less, of the entire composition, or may be 0% or less, from the viewpoint of the retention of fluoride ions.

Examples of the thickener include: sugar alcohols such as sorbitol, xylitol, erythritol, maltitol, and lactitol; glycerol, propylene glycol, polyethylene glycol having an average molecular weight of 160 to 400 (average molecular weight described in pharmaceutical sector external material standard 2006), and the like. The amount of the thickener to be blended is usually preferably 5 to 60% by weight of the entire composition.

The surfactant may be blended with an anionic surfactant, a nonionic surfactant, and an amphoteric surfactant.

Examples of the anionic surfactant include: alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate; acyl sarcosinates such as sodium lauroyl sarcosinate and sodium myristoyl sarcosinate; acyl glutamate such as sodium dodecyl benzene sulfonate, hydrogenated coconut fatty acid monoglyceride monosulfate, sodium laurylsulfate, and sodium N-palmitoyl glutamate; sodium N-methyl-N-acyl taurate, sodium N-methyl-N-acyl alaninate, sodium alpha-olefin sulfonate.

Examples of the nonionic surfactant include: polyoxyethylene alkyl ethers (for example, those having 16 to 18 carbon atoms in the alkyl group), polyoxyethylene hydrogenated castor oil (for example, those having 40 to 80 average addition moles of ethylene oxide), alkyl glucosides, polyoxyethylene polyoxypropylene block copolymers, polyglycerin fatty acid esters, sorbitan fatty acid esters, sucrose fatty acid esters, alkanolamides, polyoxyethylene sorbitan monostearate, polyoxyethylene polyoxypropylene glycols, and the like.

The amphoteric surfactants include: lauryl dimethyl amino acetic acid betaine, N-coco fatty acid acyl-N-carboxymethyl-N-hydroxyethyl ethylene diamine, coco fatty acid amidopropyl dimethyl amino acetic acid betaine, coco fatty acid amidopropyl, and the like.

The amount of the surfactant to be blended is usually preferably 0.1 to 10% by weight of the entire composition. The amount of the composition may be adjusted according to the form, purpose of use, etc., and for example, 0.1 to 10% may be incorporated into the paste-like dentifrice.

Examples of the colorant include: red No.2, red No. 3, red No. 225, red No. 226, yellow No. 4, yellow No. 5, yellow No. 205, blue No. 1, blue No.2, blue No. 201, blue No. 204, green No. 3, titanium mica, titanium oxide, and the like.

Examples of the sweetener include: saccharin sodium, aspartame, stevioside, stevia extract, p-methoxycinnamaldehyde, neohesperidin dihydrochalcone, perilla essential oil, etc.

Examples of the preservative include: parabens such as methyl paraben, ethyl paraben, butyl paraben, and the like; benzoic acid such as sodium benzoate or its salt.

The fragrances may be used in combination: natural flavors such as peppermint oil, spearmint oil, fennel oil, eucalyptus globulus oil, wintergreen oil, cinnamon oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamon oil, coriander oil, citrus oils, lyme oil, lavender oil, rosemary oil, bay oil, chamomile oil, cedar oil, marjoram oil, bay leaf oil, lemon grass oil, oregano oil, pine needle oil, neroli oil, rose oil, jasmine oil, grapefruit oil, sweet oil, grapefruit oil, iris extract, peppermint essential, rose essential oil, orange flower; the natural perfume is processed (front distillate, back distillate, fractional distillation, liquid-liquid extraction, essence, powder perfume, etc.) to obtain perfume; and single-product flavors such as menthol, carvone, anethole, eucalyptol, methyl salicylate, cinnamaldehyde, eugenol, 3-L-menthoxypropane-1, 2-diol, thymol, linalool, linalyl acetate, limonene, menthone, menthyl acetate, N-substituted-p-menthane-3-carboxamide, pinene, octanal, citral, longleaf menthone, carvone acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allyl cyclohexane propionate, methyl anthranilate, ethyl methyl phenyl glycidate, vanillin, undecalactone, hexanal, butanol, isoamyl alcohol, hexenol, dimethyl sulfide, methyl cyclopentenone, furfural, trimethyl pyrazine, ethyl lactate, ethyl thioacetate; and known flavor materials used in dentifrice compositions such as blended flavors including strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, butter flavor, milk flavor, mixed fruit flavor, and tropical fruit flavor.

The blending amount is not particularly limited, but the above-mentioned perfume raw material is preferably used in an amount of 0.000001 to 1% in the formulation composition. The flavoring agent using the above-mentioned flavoring material is preferably used in an amount of 0.05 to 2% based on the formulation composition.

The active ingredients include: bactericides such as isopropyl methylphenol, cetyl pyridinium chloride and the like; water-soluble phosphoric acid compounds such as potassium salts and sodium salts of orthophosphoric acid; enzymes such as glucanase, mutanase, amylase, and protease; tranexamic acid, epsilon-aminocaproic acid, triclosan, lysozyme chloride, allantoin chlorohydroxy aluminum, hinokitiol, ascorbic acid, tocopheryl acetate, dihydrocholesterol, alpha-bisabolol, chlorhexidine salts, and olanil; water-soluble copper compounds such as sodium copper chlorophyllin, chlorophyll, and copper gluconate; aluminum lactate, strontium chloride, potassium nitrate, berberine, hydroxamic acid or its derivative, glycyrrhizic acid or its salt, glycyrrhetinic acid or its derivative, and anticalculus agent. The above-mentioned active ingredients may be blended in an effective amount within a range that does not hinder the effects of the present invention.

Examples

The present invention will be specifically described below with reference to examples, comparative examples, and prescription examples, but the present invention is not limited to the following examples. In the following examples,% represents mass% unless otherwise specified.

Examples and comparative examples

Dentifrice compositions (paste dentifrices) having the compositions shown in tables 1 to 3 were prepared by a conventional method and evaluated by the following methods. The results are also shown in the table.

(1) Method for evaluating retention of fluorine (fluoride ion)

The retention of fluorine ions was evaluated by an adsorption test of fluorine (fluorine ions) on mucin, which is an oral mucosa component.

Into a 10mL centrifuge tube, 0.2g of mucin (manufactured by Sigma-Aldrich Co.) was added, and 5mL of the dentifrice composition (40-fold dilution with purified water) was further added, and the mixture was allowed to act for 3 minutes. Then, the mixture was centrifuged at 3,000rpm for 10 minutes, and the supernatant was removed. To the obtained mucin, 5mL of potassium citrate buffer was added and stirred for 1 minute, whereby fluorine ions adsorbed and retained in the mucin were forcedly eluted. The supernatant was collected by centrifugation at 3,000rpm for 10 minutes, and the concentration of fluorine (fluoride ions) contained in the solution was measured by a fluorimeter (Orion 1115000 4-Star: thermo Fisher Scientific Co., ltd.) to obtain a retained fluoride ion concentration (ppm).

The fluorine ion retention rate was calculated by the following formula.

Fluorine ion retention (%) =

{ (retained fluorine ion concentration (ppm))/(concentration of fluorine ion blended in formulation (ppm)/40) } ×100 based on the fluorine ion retention rate, the fluorine ion retention was evaluated according to the following evaluation criteria.

Evaluation criterion

And (3) the following materials: the retention rate of fluorine ions is above 50%

O: the retention rate of fluorine ions is more than 30% and less than 50%

Delta: the retention rate of fluorine ions is more than 20% and less than 30%

X: the retention rate of fluorine ions is less than 20 percent

(2) Method for evaluating fluorine (fluoride ion) releasing property

The release amount (release rate) and the sustained release property of fluoride ions released from mucin into saliva were evaluated for the composition (examples 1 to 14) of the composition (1) of the composition of delta or more.

Into a 10mL centrifuge tube, 0.2g of mucin (manufactured by Sigma-Aldrich Co.) was added, and 5mL of the dentifrice composition (40-fold dilution with purified water) was further added, and the mixture was allowed to act for 3 minutes. Then, the mixture was centrifuged at 3,000rpm for 10 minutes, and the supernatant was removed.

To the mucin obtained, 5mL of artificial saliva (CaCl) was added ₂ ＝1.5mmol/L、KH ₂ PO ₄ =5.0 mmol/L, acetic acid=100 mol/L, naCl =100 mol/L, balance = water; ph=7.0) and stirred for 1 minute, and allowed to stand for 3 minutes, 60 minutes, or 180 minutes to dissolve out the fluoride ions adsorbed and retained on mucin, and then centrifuged at 3,000rpm for 10 minutes, respectively, to collect the supernatant, and the supernatant was analyzed by a fluoride ion analyzer (Orion 1115000 4-Star: thermo Fisher Scientific) were measured to obtain the respective released fluorine ion concentrations.

Based on the released fluoride ion concentration, the fluoride ion release rate was calculated by the following formula.

Fluoride ion release rate (%) =

{ (released fluoride ion concentration (ppm))/(retained fluoride ion concentration (ppm)) } ×100

Based on the calculated fluoride ion release rate, the fluoride release property (release amount) was evaluated.

The compositions (examples 1 to 14) evaluated had fluoride ion release rates of less than 20% after 3 minutes of standing, and had fluoride ion release rates of 20 to 60% after 60 minutes of standing, and it was confirmed that the compositions were not released immediately but had sustained release properties.

Fluorine release was evaluated based on the fluorine ion release rate after 180 minutes of standing, according to the following evaluation criteria. The fluorine ions adsorbed and retained on mucin were gradually released by saliva, and the fluorine release was judged to be acceptable.

Evaluation criterion

And (3) the following materials: the fluoride ion release rate after standing for 180 minutes is more than 70 percent

O: the fluoride ion release rate after 180 minutes of standing is more than 50% and less than 70%

Delta: the fluoride ion release rate after 180 minutes of standing is more than 20% and less than 50%

X: the fluoride ion release rate after 180 minutes of standing is less than 20 percent

(3) Method for evaluating storage stability

(3-1) method for evaluating liquid separation stability (whether liquid separation is present or not after storage) of preparation

A3-branch container (raw material: laminated tube (manufactured by Dai Japanese printing Co., ltd.) having an innermost layer composed of linear low-density polyethylene and having a diameter of 26mm was filled with 50g of each of the dentifrice compositions, and the container was stored at 40℃for 1 month. After storage, the dentifrice composition was extruded from each tube container onto paper, and the state of liquid separation was determined according to the following scale. The average score of 3 branches was obtained, and the liquid separation stability of the preparation was evaluated according to the following evaluation criteria.

Scoring benchmark

4, the following steps: completely free of liquid separation

3, the method comprises the following steps: the mouth is slightly visible to liquid separation but to a level where there is no problem

2, the method comprises the following steps: visible separation of liquids from the surface of the paste

1, the method comprises the following steps: the degree of dripping of the separating liquid is visible when the toothpaste is extruded from the tube

Evaluation criterion

And (3) the following materials: average score of 4.0 minutes

O: the average score is more than 3.0 and less than 4.0

Delta: the average score is more than 2.0 and less than 3.0

X: average score less than 2.0

(3-2) method for evaluating curing stability (whether curing after storage) of preparation

A3-branch container (raw material: laminated tube (manufactured by Dai Japanese printing Co., ltd.) having an innermost layer composed of linear low-density polyethylene and having a diameter of 26mm was filled with 50g of each of the dentifrice compositions, and the container was stored at 40℃for 1 month. After storage, the dentifrice composition was extruded from each tube container, and the cured state was determined according to the following scale. The average score of 3 branches was obtained, and the curing stability of the formulation was evaluated according to the following evaluation criteria.

Scoring benchmark

4, the following steps: completely without curing

3, the method comprises the following steps: the mouth is slightly visible cured but at a level where there is no problem

2, the method comprises the following steps: curing of visible mouthpieces and paste surfaces

1, the method comprises the following steps: it can be seen that the curing is to such an extent that the toothpaste cannot be extruded from the tube

Evaluation criterion

And (3) the following materials: average score of 4.0 minutes

O: the average score is more than 3.0 and less than 4.0

Delta: the average score is more than 2.0 and less than 3.0

X: average score less than 2.0

Details of the raw materials used are as follows.

(A) Potassium pyrophosphate; manufactured by Taiping chemical industry Co Ltd

(A) Sodium tripolyphosphate; manufactured by Taiping chemical industry Co Ltd

(B) Calcium glycerophosphate; manufactured by Shicheng pharmaceutical Co Ltd

(C) Sodium fluoride; STELLACHEMIFA Co., ltd

(D) Hydroxyethyl cellulose dimethyl diallyl ammonium chloride; CELQUAT L-200, manufactured by Akzo Nobel Co., ltd., viscosity of 2% aqueous solution: 35-350 mPa.s (weight average molecular weight 250,000 ～ 350,000 based on Gel Permeation Chromatography (GPC) with polyethylene glycol as standard substance, rotor No.2, 20 rpm, 20 ℃ C., measurement time 1 min)

TABLE 1

TABLE 2

TABLE 3

Details of the perfume composition used are shown in tables 4 to 12. In the above examples, the evaluation results were the same even when the fragrance compositions B to P were used instead of the fragrance composition a, and the same applies to the prescription examples described later.

TABLE 4

TABLE 5

Spice 1	Parts by mass
		Linalool	1
Menthofuran	1
		Anethole	1
Menthone	1
		Menthyl acetate	1
Totalizing	5

TABLE 6

TABLE 7

Spice 3	Parts by mass
		Fennel oil	1
Eucalyptus globulus oil	1
		Cinnamon oil	1
Clove oil	1
		Thyme oil	1
Salvia oil	1
		Amomum cardamom oil	1
Coriander oil	1
		Rosemary oil	1
Laurel oil	1
		Chamomile oil	1
Cedarwood oil	1
		Basil oil	1
Totalizing	13

TABLE 8

Spice 4	Parts by mass
		Wintergreen oil	1
Dairy oil	1
		Lavender oil	1
Neroli oil (orangeflower oil)	1
		Lemon grass oil	1
Jasmine oil	1
		Rose oil	1
Iris flower oil	1
		Vanilla herb	1
Totalizing	9

TABLE 9

Spice 5	Parts by mass
		Menthyl lactate	1
N-ethyl-2-isopropyl-5-methylcyclohexane carboxamide	1
		N- [ (ethoxycarbonyl) methyl) -p-menthane-3-carboxamide	1
N-p-benzyl cyanide menthane carboxamide	1
		N- (2- (pyridin-2-yl) ethyl) -3-p-menthane carboxamide	1
3-L-menthoxypropane-1, 2-diol	1
		Peppermint glyceryl ethers	1
Huajusu (spilanthol)	1
		Menthyl succinate	1
Linalool oxide	1
		Vanillylbutyl ether	1
Isopulegol	1
		Chilli extract	1
Ginger extract	1
		Pepper extract	1
Japanese mountain pepper extract	1
		Totalizing	16

TABLE 10

Spice 6	Parts by mass
		Maltol	1
Ethyl maltol	1
		Vanillin	1
Ethyl vanillin	1
		Furanones	1
Ethylcyclopentenolone	1
		3-hydroxy-4, 5-dimethylfuran-2-one	1
Methyl cyclopentenolone	1
		2-methylbutyric acid	1
Acetic acid	1
		Propionic acid	1
Totalizing	11

TABLE 11

Perfume 7	Parts by mass
		P-methoxy cinnamic aldehyde	1
Cis-3-hexenol	1
		Trans-2-hexenal	1
Undecalactone	1
		Decalactone	1
Butyric acid ethyl ester	1
		Isoamyl acetate	1
Benzaldehyde	1
		Hexyl acetate	1
2-Methylbutanoic acid ethyl ester	1
		Benzyl alcohol	1
Alpha-terpineol	1
		Linalyl acetate	1
Phenyl glycidyl acid ethyl ester	1
		Phenethyl alcohol	1
Allyl caproate	1
		Octanol (octanol)	1
Cinnamic acid methyl ester	1
		Methyl heptynylcarboxylate (Methyl heptine carbonate)	1
Ionone (Violet)	1
		Beta-methylthiopropionic acid ethyl ester	1
Cis-6-nonenol	1
		Carane ketone	1
Jasmonate methyl ester	1
		Totalizing	24

TABLE 12

Solvent(s)	Parts by mass
		Ethanol	1
Propylene glycol	1
		Glycerol fatty acid ester	1
Glyceryl triacetate	1
		Totalizing	4

The example of the recipe is shown. The raw materials used are the same as described above.

Prescription example gel-like dentifrice

(A) /(C) (molar ratio): 0.28

(B) /(C) (molar ratio): 0.50

(A) Weight ratio/(D): 14

(B) Weight ratio/(D): 16

(C) Weight ratio/(D): 6.4

Claims (6)

1. A dentifrice composition containing: (A) Water-soluble polyphosphate, (B)Calcium glycerophosphate, (C)Water-soluble fluorine-containing compounds as well as (D) Cationized cellulose. 2. The dentifrice composition according to claim 1, wherein the component (A) is potassium pyrophosphate. The dentifrice composition according to claim 1 or 2, wherein (A)/(C) is 0.05 to 1 in molar ratio. 4. The dentifrice composition according to any one of claims 1 to 3, wherein (B)/(C) is 0.05 to 1.5 in molar ratio. 5. The dentifrice composition according to any one of claims 1 to 4, wherein the content of component (A) is 0.1 to 1.5% by mass, and the content of component (B) is 0.1 to 2% by mass, ( The content of component C is 500 to 5000 ppm in terms of fluoride ions, and the content of component (D) is 0.01 to 0.5% by mass. 6. The dentifrice composition according to any one of claims 1 to 5, which is a paste dentifrice or a gel dentifrice.