WO2018066341A1

WO2018066341A1 - Oral composition and method for suppressing discoloration of formulation and liquid separation thereof

Info

Publication number: WO2018066341A1
Application number: PCT/JP2017/033453
Authority: WO
Inventors: 祐輔吉田
Original assignee: ライオン株式会社
Priority date: 2016-10-06
Filing date: 2017-09-15
Publication date: 2018-04-12
Also published as: JP2018058795A

Abstract

Provided is an oral composition comprising (A) hinokitiol, (B) ascorbic acid phosphate or a salt thereof, and (C) fluorine ion, wherein the content of component (C) is 0.0001 to 0.27% by mass, and ((A)+(B))/(C) which represents the mixing ratio of components (A) and (B) with respect to component (C) is 0.5 to 11000 as a mass ratio. Also provided is a method for suppressing discoloration of formulations and liquid separation in an oral composition that comprises components (A) and (B) due to components (A) and (B), wherein component (C) is compounded in the specified range into the oral composition, and components (A), (B), and (C) are compounded within the specified range in the ratio, ((A)+(B))/(C).

Description

Oral composition and method for inhibiting discoloration and liquid separation thereof

The present invention relates to an oral composition containing hinokitiol and having excellent appearance stability over time, and a method for inhibiting formulation discoloration and liquid separation in the oral composition.

Hinokitiol is often used in oral compositions such as dentifrices as a natural product-derived ingredient that has antibacterial and bactericidal effects on periodontal disease-causing bacteria in the oral cavity, but it causes discoloration of the preparation and phase separation. The problem is known. Patent Document 1 (Japanese Patent No. 5600872) proposes that discoloration and phase-liquid separation of a hinokitiol-containing toothpaste composition can be suppressed by a specific combination of edetic acid, ethanol and water. In Patent Document 2 (Japanese Patent Laid-Open No. 11-130648), coloring and remaining rate reduction can be suppressed by blending water-soluble sulfites with a weakly alkaline oral composition containing a water-soluble inorganic carbonate and hinokitiol. Proposed. In Patent Document 3 (Japanese Patent Application Laid-Open No. 2002-3354), a decrease in the residual rate of hinokitiol can be suppressed by filling an oral tube composition containing hinokitiol into an aluminum tube coated with a resin selected from a phenol resin and a butyral resin. Has been proposed.

On the other hand, ascorbic acid phosphate ester such as magnesium ascorbate or a salt thereof is a medicinal component for oral compositions, but is also known as a component with problems such as discoloration of preparations. JP-A-11-286422 and JP-A-2000-256152 have proposed oral compositions containing acid esters in which discoloration is suppressed. However, it is not known that the ascorbic acid derivative itself has a discoloration suppressing effect.

Japanese Patent No. 5600872 JP-A-11-130648 JP 2002-3354 A JP-A-11-286422 JP 2000-256152 A

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide an oral composition containing hinokitiol and having excellent appearance stability over time.

As a result of diligent studies to achieve the above object, the present inventor has further added fluoride ions to the oral composition containing both hinokitiol and ascorbic acid phosphate ester or salts thereof, both of which have coloring problems. It was found that, when blended in a specific amount and proportion, coloring was suppressed, and the appearance of liquid separation by the combined use system was prevented, excellent appearance stability was given over time, and a good feeling of use could be imparted. . That is, in the present invention, it contains (A) hinokitiol, (B) ascorbic acid phosphate ester or salt thereof, and (C) fluorine ion, and the content of (C) component is 0.0001 to 0.27% by mass. The composition for oral cavity in which ((A) + (B)) / (C) indicating the blending ratio of the components (A) and (B) to the component (C) is 0.5 to 11,000 as a mass ratio The product was found to have excellent appearance stability over time and good usability (astringency, bitterness, tastelessness) and led to the present invention.

More specifically, when the present inventor combined hinokitiol with an ascorbic acid ester or a salt thereof in an oral composition, a complex was formed by the interaction between the two, thereby causing discoloration of the preparation and Liquid separation deteriorated. In addition, the combined use of the two causes a new problem that astringency, bitterness, and off-taste are strongly expressed and the taste deteriorates. Therefore, as a result of further investigation to solve the above problems, the present inventor has combined the component (C) with the combination system of the components (A) and (B), and the content of the component (C) and (( The mass ratio of A) + (B)) / (C) was within a specific range, and the discoloration and liquid separation of the preparation were suppressed over time, and the taste was also improved. In particular, the unique and exceptional problem that the problem of discoloration that cannot be achieved simply by blending the (A) component and the (C) component can be solved by using a three-component system including the (B) component having the same discoloration problem. It was possible to give a good effect. Thereby, as is clear from the results of Examples and Comparative Examples described later, according to the present invention, it is sufficient that the preparation is discolored without causing significant discoloration even after storage at 50 ° C. for 1 month. An excellent discoloration suppressing effect that suppresses and an excellent liquid separation suppressing effect that sufficiently suppresses without causing significant liquid separation of 1 cm or more when extruded from a container accommodated even after storage at 50 ° C. for 1 month, and ( Astringent taste, bitter taste, and off-flavor produced by the combined use of components A) and (B) can be suppressed to give a good feeling of use.

Therefore, the present invention
[I] (A) Hinokitiol,
(B) Ascorbic acid phosphate or a salt thereof,
(C) Fluorine ions are contained, the content of component (C) is 0.0001 to 0.27% by mass, and the blending ratio of components (A) and (B) to component (C) is shown (( A composition for oral cavity, wherein A) + (B)) / (C) is a mass ratio of 0.5 to 11,000, and [II] (A) hinokitiol and (B) ascorbic acid phosphate An oral composition containing an ester or a salt thereof, (C) 0.0001 to 0.27% by mass of fluorine ions, and the blending ratio of the components (A) and (B) to the component (C) (( A preparation comprising the components (A) and (B) in the composition for oral cavity, wherein A) + (B)) / (C) is blended in a mass ratio of 0.5 to 11,000. A method for suppressing discoloration and liquid separation is provided.

According to the present invention, it is possible to provide a composition for oral cavity containing hinokitiol and ascorbic acid phosphate or a salt thereof, which has excellent appearance stability over time and good usability (astringency, bitterness, tastelessness). . The oral composition of the present invention has a high preventive or ameliorating effect on periodontal diseases, and is useful for preventing or improving periodontal diseases.

Hereinafter, the present invention will be described in further detail. The composition for oral cavity of this invention contains (A) hinokitiol, (B) ascorbic acid phosphate ester or its salt, and (C) fluorine ion.

(A) Hinokitiol is a unique component contained in Aomori Hiba, a natural tree, and is a crystalline acidic compound. Other tree species containing hinokitiol include Taiwan cypress, North American Western red cedar and the like. Hinokitiol has strong antibacterial activity and a broad antibacterial spectrum, is one of the few natural fungicides, and has an effect of preventing or improving periodontal diseases. In addition, hinokitiol includes a chemically synthesized product, and in the present invention, a natural product or a synthetic product may be used. Such hinokitiol is widely used in foods, cosmetics, pharmaceuticals, agricultural supplies, building materials, baits, etc., and in the present invention, commercially available products used for these can be used. it can.

(A) The amount of hinokitiol is preferably 0.005 to 0.5% (mass%, the same applies hereinafter) of the whole composition, more preferably 0.01 to 0.2%. As the blending amount increases, the effect of preventing or improving periodontal disease increases, but when it is 0.5% or less, the feeling of use (astringency, bitterness, and taste) can be maintained sufficiently and satisfactorily.

(B) Ascorbic acid phosphates include those in which one or more of the hydroxyl groups at positions 2, 3, 5, and 6 of ascorbic acid are converted to phosphates, for example, ascorbic acid-2- Examples thereof include phosphoric acid ester, ascorbic acid-3-phosphate ester, ascorbic acid-6-phosphate ester and the like. Examples of these salts include sodium salt, potassium salt, calcium salt, magnesium salt and the like. 1 type (s) or 2 or more types chosen from these can be used as (B) ascorbic acid phosphate ester or its salt. In particular, from the viewpoint of the stability of the composition, a derivative in which the hydroxyl group at the 2-position or 3-position of ascorbic acid is converted to a phosphate ester is preferable, and a magnesium salt or sodium salt of ascorbyl 2-phosphate ester is more preferable. Particularly preferred is a magnesium salt.

(B) The blending amount of ascorbic acid phosphate or a salt thereof is preferably 0.1 to 5%, more preferably 0.2 to 4% of the entire composition. When it is 0.1% or more, the effect of suppressing discoloration and liquid separation of the present invention is particularly excellent. When it is 5% or less, the effect of suppressing discoloration and liquid separation is particularly good.

(C) Fluorine ions can be blended as a fluorine-containing compound that supplies fluorine ions. Examples of the fluorine-containing compound include sodium fluoride, sodium monofluorophosphate, tin fluoride and the like, and one or more selected from these can be used. In particular, sodium fluoride and sodium monofluorophosphate are preferable from the viewpoint of imparting the effect of the present invention, and sodium monofluorophosphate is more preferable.

The blending amount of (C) fluorine ions is 0.0001 to 0.27%, preferably 0.001 to 0.19% of the entire composition. The fluorine-containing compound is blended within the range of the blending amount of the fluorine ions, and the blending amount can be obtained by conversion from the fluorine ion amount. For example, in the case of sodium monofluorophosphate, the preferable blending amount is 0.001 to 2%, particularly 0.01 to 1.4% of the whole composition. In the case of sodium fluoride, the preferred blending amount is 0.0003 to 0.58%, particularly 0.001 to 0.41% of the entire composition.
(C) When the compounding quantity of a fluorine ion is in the above range, the discoloration suppressing effect and the liquid separation suppressing effect of the preparation are excellent, and the feeling of use (astringency, bitterness, tastelessness) is improved. If it is less than 0.0001%, the discoloration suppressing effect or the separation suppressing effect cannot be obtained satisfactorily, and the feeling of use (astringency, bitterness, tastelessness) is inferior. If it exceeds 0.27%, the effect of suppressing liquid separation is lowered, and the feeling of use (astringency, bitterness, tastelessness) is inferior.

In the present invention, ((A) + (B)) / (C) indicating the ratio of the total blending amount of the components (A) and (B) to the blending amount of the fluorine ion of the component (C) is 0 as a mass ratio. 0.5 to 11,000, preferably 0.6 to 10,500, more preferably 1.2 to 4,200. Within this range, the discoloration-suppressing effect and liquid separation-suppressing effect of the preparation are excellent, and the feeling of use (astringency, bitterness, tastelessness) is excellent. If ((A) + (B)) / (C) is less than 0.5, the effect of suppressing liquid separation is reduced, and the feeling of use (astringency, bitterness, and taste) is inferior. If it exceeds 11,000, the discoloration suppressing effect and the liquid separation suppressing effect of the preparation are lowered, and the feeling of use (astringency, bitterness, tastelessness) is inferior.

The oral composition of the present invention is not limited in its shape and dosage form, but in particular, it is prepared in a semi-solid form such as paste or gel and used as a dentifrice such as toothpaste or gel toothpaste, especially toothpaste. Can be suitably prepared.

In the composition for oral cavity of the present invention, in addition to the above-mentioned components, known oral additive components (pharmacologically acceptable carriers) according to the dosage form and the like within a range not impairing the effects of the present invention Can be blended. As an additive component, in dentifrices, for example, abrasives, binders, surfactants, wetting agents, coloring agents, preservatives, sweeteners, fragrances, pH adjusters, (A), (B), (C) Examples include active ingredients other than the ingredients. Although the specific example of an additional component is shown below, the component which can be mix | blended with the composition for oral cavity of this invention is not restrict | limited to these.

As abrasives, silica-based abrasives such as silica gel, precipitated silica, anhydrous silicic acid, aluminosilicate, zirconosilicate, calcium pyrophosphate, calcium carbonate, aluminum hydroxide, alumina, magnesium carbonate, tribasic magnesium phosphate, zeolite, Examples thereof include zirconium silicate, hydroxyapatite, and a synthetic resin abrasive. The blending amount of the abrasive is usually 2 to 40%, particularly 10 to 25% of the whole composition.
In the present invention, a silica-based abrasive is preferred as the abrasive, particularly in terms of suppressing discoloration of the preparation, and a silica-based abrasive is particularly preferred as the main abrasive. Further, abrasives other than silica-based abrasives may not be blended, but when blended, the blending amount is 10% or less, particularly 1 to 8% is preferable, and not blended (0%) is more preferable.

As a binder, gums such as sodium polyacrylate, xanthan gum, guar gum, carboxymethylcellulose sodium, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxymethylethylcellulose, methylcellulose, cellulose derivatives such as cationized cellulose, carrageenan, Examples include sodium alginate, montmorillonite, and gelatin. Especially, the 1 type or 2 types chosen from a xanthan gum and a sodium polyacrylate from the point of the expression of the liquid-separation inhibitory effect is preferable. The amount of the binder is usually 0.1 to 10%, particularly 0.5 to 5% of the whole composition.

As the surfactant, an anionic surfactant, a cationic surfactant, a nonionic surfactant, and an amphoteric surfactant can be used. Specific examples include the following.
Anionic surfactants: alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, sodium dodecylbenzene sulfonate, hydrogenated coconut fatty acid monoglyceride sodium monosulfate, sodium lauryl sulfoacetate, sodium α-olefin sulfonate, sodium lauroyl sarcosine , Acylamino acid salts such as lauroylmethyltaurine, α-sulfo fatty acid alkyl ester / sodium, alkyl phosphate ester cationic surfactant: distearylmethylammonium chloride, stearyldimethylbenzylammonium chloride Nonionic surfactant: sorbitan fatty acid Esters, sugar alcohol fatty acid esters such as polyoxyethylene sorbitan fatty acid ester, sucrose fatty acid ester, glycerin fat Esters, polyglycerin fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyhydric alcohol fatty acid esters such as polyethylene glycol fatty acid esters, polyoxyethylene polyoxypropylene copolymers, polyoxyethylene alkylphenyl ether, polyoxyethylene alkyl ether, poly Ether type surfactants such as oxyethylene hydrogenated castor oil, fatty acid alkanolamides such as lauric acid diethanolamide Amphoteric surfactants: imidazoliums such as 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolium betaine N-alkyldiaminoethylglycine surfactant content such as betaine, N-lauryldiaminoethylglycine, N-myristyldiaminoethylglycine, etc. 0.2 to 15%, especially 0.5 to 10% of the total composition.

Examples of the wetting agent include propylene glycol, pentylene glycol, hexylene glycol, octylene glycol, polyethylene glycol having an average molecular weight of 200 to 6,000 (average molecular weight described in Quasi-drug Raw Material Standard 2006), ethylene glycol, 1,3 -Polyhydric alcohols such as butylene glycol and glycerin, sugar alcohols such as sorbitol, xylitol, erythritol, and reduced starch saccharified product. The amount of the wetting agent is usually 5 to 50%, particularly 20 to 45% of the whole composition.

As colorants, legal dyes such as blue No. 1, yellow No. 4 and green No. 3, natural dyes such as caramel, titanium oxide, etc., as preservatives, paraoxybenzoic acid esters or salts thereof, benzoic acid or salts thereof, etc. Is mentioned.
Examples of the sweetening agent include saccharin sodium, aspartame, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidyl dihydrochalcone, perilartin and the like.

As the fragrance, those known as oral fragrances can be used. For example, menthol, anethole, carvone, eugenol, limonene, n-decyl alcohol, citronellol, α-terpineol, citronellyl acetate, cineol, linalool, ethyl linalool, vanillin, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, Examples include sage oil, rosemary oil, cinnamon oil, pimento oil, cinnamon oil, perilla oil, winter green oil, clove oil, eucalyptus oil and the like. The blending amount of the fragrance is preferably 0.000001 to 2% of the entire composition.

Examples of the pH adjuster include organic acids such as citric acid, lactic acid, malic acid and salts thereof, and inorganic compounds such as hydrochloric acid, sodium hydroxide, potassium hydroxide, disodium hydrogen phosphate, sodium dihydrogen phosphate, and the like. .
The pH (25 ° C.) of the composition is preferably 8 or more, particularly 8.1 to 9.3, particularly from the viewpoint of the stability of the component (B).

In the oral composition of the present invention, water is used as a solvent. The lower monohydric alcohol such as ethanol may be added in an amount of about 1 to 10%, but may not be added (0%). The amount of water is not particularly limited, and can usually be in the range of 5 to 95% by mass. In particular, when the oral composition of the present invention is a dentifrice, it can be preferably 5 to 70%, more preferably 10 to 60%.

Hereinafter, although an Example, a comparative example, and a formulation example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, “%” means “% by mass” unless otherwise specified.

[Examples and Comparative Examples]
Oral compositions (toothpaste) having the compositions shown in Tables 1 and 2 were prepared by a conventional method and evaluated by the following methods. The results are shown in the table.
In addition, ((A) + (B)) / (C) in the table is a mass ratio indicating the ratio of the total blending amount of the (A) and (B) components to the blending amount of the fluorine ions of the (C) component. Yes (the same applies below).
The pH (25 ° C.) of each composition was adjusted within the range of 8.1 to 9.3 (the same applies hereinafter).
In addition, it was confirmed that the compositions for oral cavity of the Examples all have the effects of the (A) and (B) components effectively acting to sufficiently exhibit the medicinal effects, and have a high periodontal disease prevention or improvement effect.

(1) Discoloration evaluation method Three oral compositions filled in an 8 mm diameter laminated tube were stored at 50 ° C. for 1 month or −5 ° C. for 1 month, and then the oral composition on a straw half paper. The object was extruded 10 cm, and five expert panelists of the test subjects observed changes in color tone of the product stored at 50 ° C. compared to the product stored at −5 ° C., and sensory evaluation was performed according to the following four grades. The average value of the score results of five people for three was obtained and judged according to the following evaluation criteria. ○ The above was deemed acceptable because discoloration of the preparation was suppressed over time.
4 points: no discoloration 3 points: almost no discoloration 2 points: discoloration observed 1 point: remarkably discoloration evaluation criteria ◎: 3.5 points or more and 4.0 points or less ○: 3 0 point or more and less than 3.5 point △: 2.0 point or more and less than 3.0 point ×: Less than 2.0 point

(2) Evaluation method of liquid separation After storing 3 compositions of each composition for oral cavity filled in a laminate tube having a diameter of 8 mm at 50 ° C. for 1 month, the composition for oral cavity was extruded 10 cm onto a straw half paper, and the straw half paper was stained. The length of the extracted liquid was measured, and the degree of liquid separation was evaluated according to the following four grades. The average value of the three score results was obtained and judged according to the following evaluation criteria. ○ The above were deemed acceptable because liquid separation of the preparation was suppressed over time.
Criterion criteria for liquid separation 4 points: No liquid separation is observed 3 points: When extruded, there is almost no liquid separation at the mouth, and there is no problem in use 2 points: When pushed, liquid separation is 1 to 3 cm at the mouth Permitted 1 point: When extruded, liquid separation exceeds 3 cm at the mouth. Evaluation criteria ◎: 3.5 or more and 4.0 or less ○: 3.0 or more and less than 3.5 △: 2 .0 point or more and less than 3.0 point ×: less than 2.0 point

(3) Evaluation method of feeling of use (astringency, bitterness, tastelessness) A sensory test was conducted using 10 expert panelists. About 0.5 g of the oral composition was placed on a commercially available toothbrush and brushed for 3 minutes, and the astringency, bitterness, and taste of taste felt during use were sensory-evaluated according to the following four grades. The average value of the score result of 10 persons was calculated | required and it determined by the following evaluation criteria. ○ The above is said to pass well, with astringent taste, bitterness and off-flavor being suppressed.
4 points: no astringency, bitterness, or off-flavor 3 points: slight astringency, bitterness, off-flavor 2 points: slightly astringency, bitterness, off-flavor 1 : Astringency, bitterness, and off-flavor are considerable. Evaluation criteria ◎: 3.5 or more and 4.0 or less ○: 3.0 or more and less than 3.5 △: 2.0 or more and less than 3.0 ×: Less than 2.0

Details of the main raw materials used are as follows.
(A) Hinokitiol: Takasago Fragrance Co., Ltd. (B) L-Ascorbyl Magnesium Phosphate: Wako Pure Chemical Industries, Biochemical (C) Sodium Monofluorophosphate: Rhodia Nikka Co., Ltd. ( C) Sodium fluoride: sodium fluoride manufactured by Stella Chemifa Corporation

Note: The composition for oral cavity of Reference Example did not cause liquid separation over time, and did not develop astringency, bitterness or off-taste, and had a good feeling of use.

A prescription example is shown below.

[Prescription Example 1] Toothpaste (A) Hinokitiol 0.1%
(B) L-ascorbyl magnesium phosphate 0.3
(C) Sodium monofluorophosphate 0.73
Fluorine ion content 0.096
Silicic anhydride (abrasive) 12
Sorbit liquid (70%) 40
Saccharin sodium 0.2
Thickening silica 6
Titanium oxide 0.5
Propylene glycol 3
Xanthan gum 0.7
Sodium polyacrylate 0.4
Citric acid 0.1
Sodium hydroxide 0.1
Sodium lauryl sulfate 1.5
Fragrance 0.8
Purified water balance
Total 100.0%
((A) + (B)) / (C) = 4.2

Claims

(A) Hinokitiol,
(B) Ascorbic acid phosphate or a salt thereof,
(C) Fluorine ions are contained, the content of component (C) is 0.0001 to 0.27% by mass, and the blending ratio of components (A) and (B) to component (C) is shown (( A composition for oral cavity, wherein A) + (B)) / (C) is 0.5 to 11,000 as a mass ratio.
The composition for oral cavity according to claim 1, wherein the component (B) is an ascorbic acid phosphate magnesium salt.
(C) The composition for oral cavity according to claim 1 or 2, wherein the source of fluorine ions is one or more fluorine-containing compounds selected from sodium fluoride, sodium monofluorophosphate and tin fluoride.
The blending amount of component (A) is 0.005 to 0.5 mass% in the composition, and the blending amount of component (B) is 0.1 to 5 mass% in the composition. The composition for oral cavity according to item.
The oral composition according to any one of claims 1 to 4, further comprising 2 to 40% by mass of a silica-based abrasive.
The composition for oral cavity according to claim 5, wherein the content of the abrasive other than the silica-based abrasive is 0 to 10% by mass.
The oral composition according to any one of claims 1 to 6, which is a dentifrice composition.
(A) 0.001 to 0.27% by mass of fluorine ions in (C) component and (A) the component for oral cavity containing hinokitiol and (B) ascorbic acid phosphate or salt thereof And (B) component ratio ((A) + (B)) / (C) is blended within the range of 0.5 to 11,000 as a mass ratio. A method for suppressing discoloration and liquid separation by the components (A) and (B) in the product.
The method for suppressing discoloration and liquid separation according to claim 8, wherein the composition for oral cavity further comprises (D) 2-40% by mass of a silica-based abrasive.