JP5600872B2 - Toothpaste composition - Google Patents

Description

The present invention relates to a toothpaste composition having excellent stability of hinokitiol, high antibacterial activity, no discoloration and no phase separation, and excellent storage stability over time.

  The cause of the two major oral diseases of caries and periodontal disease is thought to be due to various bacteria in the oral plaque. In particular, caries is streptococcus such as Streptococcus mutans (S. mutans), teeth Peripheral disease is an infection caused by bacteria such as obligate anaerobic gram-negative bacilli such as P. gingivalis, and the cause of bad breath is the oral cavity such as Fusobacterium nucleatum. Bacteria are involved. Accordingly, it is said that it is useful to control plaque control, that is, to keep the number of pathogenic bacteria in the oral cavity at a low level as an effective means for prevention and improvement of oral diseases.

  As a means for reducing the number of pathogenic bacteria in the oral cavity, hinokitiol, which is a natural antibacterial agent, has an excellent oral tissue adsorbability, high antibacterial activity and plaque formation inhibitory activity, and is an oral composition. It is known to blend into.

  However, when hinokitiol is blended with an oral composition, its antibacterial activity is reduced, storage stability is poor, and when stored for a long period of time, discoloration and phase separation occur over time.

  As means for maintaining the antibacterial activity of hinokitiol, an oral composition containing hinokitiol and a carboxylic acid type amphoteric surfactant (see Patent Document 1), hinokitiol and edetic acid or a salt thereof, and a carboxylic acid type amphoteric surface activity Oral composition blended with an agent (see Patent Document 2), Oral composition blended with hinokitiol and a readily water-soluble inorganic salt (see Patent Document 3), Oral composition blended with hinokitiol, herbal extract and allantoin The composition (refer patent document 4) and the composition for oral cavity (refer patent document 5) which mix | blended hinokitiol and eucalyptus oil are proposed.

However, in any of the techniques, it is difficult to satisfactorily exhibit the antibacterial activity derived from hinokitiol, and discoloration and phase-liquid separation occur over time, making it difficult to obtain good storage stability.
Incorporating hinokitiol into the oral composition in this way is effective as a means of preventing or improving oral diseases due to its antibacterial activity, but it suppresses discoloration and phase separation while maintaining the antibacterial activity of hinokitiol. Thus, it has been difficult for the prior art to achieve both storage stability over time.

JP 63-2111217 A JP 63-211118 A JP-A-4-198121 JP 2002-20253 A JP 2004-300088 A Japanese Patent Laid-Open No. 10-194543 JP 2006-117600 A

  The present invention has been made in view of the above circumstances, has excellent stability in preparations of hinokitiol, exhibits high antibacterial activity, suppresses discoloration and phase separation even after long-term storage, and has excellent storage stability. Another object is to provide an oral composition containing hinokitiol.

  As a result of intensive studies to achieve the above-mentioned object, the present inventors have found that an oral composition containing hinokitiol contains disodium edetate, trisodium edetate, dipotassium edetate dihydrate, edetate tetra By adding one or more edetates selected from sodium dihydrate, ethanol, and water in appropriate proportions, the stability of hinokitiol in the preparation is enhanced and high antibacterial activity is exhibited. In addition, it was found that even when stored for a long period of time, discoloration hardly occurs, and a preparation excellent in phase-liquid separation stability and storage stability over time can be obtained.

  Hinokitiol is a naturally-occurring component and crystalline acidic compound contained in Taiwan Hinoki and Aomori hiba, and is known to have strong antibacterial activity and a broad antibacterial spectrum among known naturally-occurring antibacterial components. (See Patent Documents 6 and 7). Patent Document 6 describes that the stability of glucosyltransferase inhibitory activity and antibacterial activity of moth beetle can be maintained by blending a cincin extract or hinokitiol with a composition for oral cavity containing jellyfish extract and herbal extract. Has been. Patent Document 7 discloses an oral appliance cleaning agent and an oral cavity excellent in antibacterial action and storage stability by blending lysozyme chloride with a cationic fungicide, triclosan, isopropylmethylphenol, hinokitiol, tea tree pill, and the like. It is described that a surface treatment agent for internally mounted devices can be obtained.

However, as a result of investigations by the present inventors, when hinokitiol is simply added to the oral composition, it is derived from the production equipment because of the high activity of hinokitiol, that is, due to the formation of various complex salts with metal ions of hinokitiol. The antibacterial activity of hinokitiol decreases due to binding to trace metals, etc., and because of oil-soluble components, adsorption to the inner surface of the container and phase-liquid separation occur, resulting in poor storage stability over time. It was difficult to achieve both discoloration and phase-liquid separation while maintaining the antibacterial activity.
On the other hand, by blending the above-mentioned edetate, ethanol, and water in a specific ratio to the toothpaste composition containing hinokitiol, these will become clear from the examples described later. Ingredients act synergistically, the above-mentioned decrease in antibacterial activity and adsorption to the inner surface of the container are effectively suppressed, the stability of hinokitiol is greatly improved, and its antibacterial activity is enhanced to exhibit excellent antibacterial activity In addition, discoloration and phase-liquid separation do not occur after long-term storage, and a preparation having excellent storage stability can be obtained. Incidentally, edetate are known as chelating agents, known as a blending component in the oral composition, according to the present invention, the toothpaste composition containing hinokitiol, and edetate salts, ethanol and The combined use of water and a specific ratio provides a special effect that cannot be achieved if any of the above essential requirements is lacking.

Accordingly, the present invention provides the following toothpaste compositions.
[1]
(A) 0.005-0.2 mass% of hinokitiol,
(B) edetate disodium, edetate trisodium, edetate dipotassium dihydrate, at least one of edetate selected from edetate tetrasodium dihydrate 0.1-0.5 wt%,
(C) 0.2 to 3% by mass of ethanol,
(D) is water 30-45 wt%
A toothpaste composition comprising (d) / (c) in a mass ratio of 70 to 150.
[2]
The toothpaste composition according to [1], which does not contain allantoins.

  The composition for oral cavity of the present invention is excellent in stability of hinokitiol, exhibits excellent antibacterial activity, hardly undergoes discoloration or phase-liquid separation over time even after long-term storage, and has excellent storage stability.

Hereinafter, the present invention will be described in more detail.
The oral composition of the present invention is prepared as a toothpaste such as a toothpaste, a liquid toothpaste, a liquid toothpaste, a moisturized toothpaste, a mouthwash, etc., particularly as a toothpaste, (a) hinokitiol, (b) Essentially contains edetate, (c) ethanol, and (d) water.

  As the component (a) hinokitiol, a commercially available product that is usually defined as having a purity of 98% or more can be used. For example, hinokitiol (manufactured by Takasago Incense) can be used.

The amount of cypress thiols is 0.005% to 0.2% based on the total amount of the composition in terms of antimicrobial activity and discoloration (mass%, hereinafter the same.), In particular 0.01% to 0.1% are preferred. If it is less than 0.005%, sufficient antibacterial activity is not exhibited . If it exceeds 0.2%, discoloration occurs .

  As the edetate of the component (b), edetate disodium (official name: ethylenediaminetetraacetic acid disodium, abbreviated name: EDTA sodium), edetate trisodium, edetate dipotassium dihydrate, edetate tetrasodium dihydrate One kind or two or more kinds selected from salts are used, and disodium edetate is particularly preferable.

  As the edetate, commercially available products can be used. For example, disodium edetate is disorbin NA2 (manufactured by Lion Corporation), trisodium edetate is zonone T (manufactured by Daiichi Chemicals), edetic acid As dipotassium dihydrate, Kirest 2K-SD (manufactured by Kirest Co., Ltd.) can be used, and as edetate tetrasodium dihydrate, Zonone N (Daiichi Chemical Co., Ltd.) can be used.

  The blending amount of the component (b) edetate is 0.02 to 1%, preferably 0.1 to 0.5%, based on the total amount of the composition in terms of antibacterial activity, discoloration and phase-liquid separation. If it is less than 0.02%, sufficient antibacterial activity and discoloration suppressing effect are not exhibited, and if it exceeds 1%, phase-liquid separation occurs or irritation occurs to the oral mucosa.

(C) The ethanol of a component can use a commercial item, for example, ethanol (made by Nippon Alcohol Sales). In addition, although ethanol may be mix | blended in a fragrance | flavor and other formulation compounding components, you may add separately as a compounding component, but the total compounding amount of ethanol is 0.2 to 3 % of the whole composition, Preferably Is 0.3 to 3%. If it is less than 0.2%, a sufficient discoloration suppressing effect cannot be exhibited . If it exceeds 10%, phase liquid separation or irritation to the oral mucosa may occur.

(C) The mixing ratio of (d) water to ethanol ((d) / (c)) is 10 to 150, more preferably 70 to 130 in terms of mass ratio from the viewpoint of discoloration and phase-liquid separation. When the blending ratio is less than 3, phase-liquid separation occurs, and when it exceeds 200, a sufficient discoloration suppressing effect is not exhibited.
In addition, although the water content in a composition should just satisfy | fill the said mixture ratio, 20 to 50%, especially 30 to 45% are preferable.

  The composition for oral cavity of the present invention can be blended with other known additives in addition to the above essential components in a range not impeding the effects of the present invention, depending on the dosage form and the like. For example, in the case of toothpaste, abrasives, thickeners, binders, surfactants, and sweeteners, preservatives, active ingredients, pigments, fragrances, etc. can be blended as necessary. It can mix and can manufacture by a normal method.

  As an abrasive, anhydrous silica, silica gel, aluminosilicate, zirconosilicate, dicalcium phosphate dihydrate, dibasic calcium phosphate anhydride, calcium pyrophosphate, aluminum hydroxide, alumina, titanium dioxide, crystalline zirconium silicate, Polymethyl methacrylate, insoluble calcium metaphosphate, light calcium carbonate, heavy calcium carbonate, magnesium carbonate, tertiary magnesium phosphate, zeolite, zirconium silicate, tertiary calcium phosphate, hydroxyapatite, fluoroapatite, calcium deficient apatite, tertiary calcium phosphate , Tetracalcium phosphate, eighth calcium phosphate, synthetic resin-based abrasive and the like (usually 2 to 50%, particularly 10 to 40%).

  As the thickener, one or two or more kinds of polyhydric alcohols such as glycerin, sorbit, propylene glycol, polyethylene glycol having a molecular weight of 200 to 6000, ethylene glycol, and reduced starch saccharified product can be used (usually 5 to 5). 50%).

  As binder, organic binders such as sodium polyacrylate, xanthan gum, sodium alginate, propylene glycol alginate, carboxymethylcellulose sodium, hydroxyethylcellulose, carbopol, guar gum, gelatin, Avicel, montmorillonite, kaolin, bentonite, etc. Examples thereof include inorganic binders (normally 0 to 5%, particularly 0.1 to 3%).

  As the surfactant, as an anionic surfactant, for example, sodium lauryl sulfate, lauroyl sarcosine sodium, polyoxyethylene alkyl sulfate, N-lauroyl taurine salt, α-olefin sulfonate, etc. Nonionic surfactants such as N-acyl glutamate, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, etc., for example, alkyl glycosides, sucrose fatty acid esters, alkylol amides, polyoxyethylene sorbitan monostearate Rate, polyoxyethylene polyoxypropylene glycol, polyoxyethylene alkyl ether, decaglyceryl laurate and the like (usually 0.1 to 3%, particularly 0.5 to 2%).

  Sweeteners include saccharin sodium, aspartame, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidyl dihydrochalcone, perilartin, etc., and preservatives include parabens (paraoxybenzoate) such as butylparaben and ethylparaben. And sodium benzoate.

  Various active ingredients include: fluorides such as sodium fluoride, potassium fluoride, stannous fluoride, strontium fluoride, sodium monofluorophosphate, and water-soluble phosphate compounds such as orthophosphoric acid potassium salt and sodium salt. , Tranexamic acid, epsilon-aminocaproic acid, allantoin chlorohydroxyaluminum, ascorbic acid, dl-tocopherol acetate, dihydrocholesterol, α-bisabolol, chlorhexidine salts, azulene, glycyrrhetin, sodium chloride, glycyrrhetinic acid, copper chlorophyllin sodium, chlorophyll, glycerophosphate Chelating phosphate compounds such as copper gluconate, copper compounds such as copper gluconate, aluminum lactate, strontium chloride, potassium nitrate, hydroxamic acid and its derivatives, sodium tripolyphosphate , Zeolites, methoxyethylene, epidihydrocholesterin, benzethonium chloride, dihydrocholesterol, trichlorocarbanilide, zinc citrate, sweet cherry extract, duckweed extract, chamomile, clove, rosemary, red gon, safflower etc. It is done. In addition, the compounding quantity of these active ingredients can be made into an effective quantity in the range which does not prevent the effect of this invention.

  Perfumes are peppermint oil, spearmint oil, anise oil, eucalyptus oil, wintergreen oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamom oil, coriander oil, mandarin oil, lime Oil, lavender oil, rosemary oil, laurel oil, camomil oil, caraway oil, marjoram oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, iris concrete, absolute peppermint Natural fragrances such as absolute rose and orange flower, and fragrances that have been processed (front reservoir cut, rear reservoir cut, fractional distillation, liquid-liquid extraction, essence, powder fragrance, etc.), and Menthol, Carvone, Anethole, Cineol, Methyl salicylate , Synamic aldehyde, eugenol, 3-l-menthoxypropane-1,2-diol, thymol, linalool, linalyl acetate, limonene, menthone, menthyl acetate, N-substituted-paramentane-3-carboxamide, pinene, octylaldehyde , Citral, pulegone, carbyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allyl cyclohexane propionate, methyl anthranilate, ethyl methyl phenyl glycidate, vanillin, undecalactone, hexanal, propyl alcohol, butanol, isoamyl Alcohol, hexenol, dimethyl sulfide, cycloten, furfural, trimethylpyrazine, ethyl lactate, methyl lactate, ethylthioacete For peroral compositions such as strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, butter flavor, milk flavor, fruit mix flavor, tropical fruit flavor, etc. The well-known perfume material used can be used.

  The blending amount of the fragrance is not particularly limited, however, the above fragrance material is preferably used in a composition of 0.000001 to 1%. Moreover, it is preferable to use 0.1-2.0% of the fragrance | flavor for perfume using the said fragrance | flavor raw material in a formulation composition.

  Examples of the colorant include Blue No. 1, Responsible Color No. 4, Green No. 3, and the like.

  The material in particular of the container which accommodates the composition for oral cavity of this invention is not restrict | limited, Usually, the container used for the composition for oral cavity can be used. Specifically, plastic containers such as polyethylene, polypropylene, polyethylene terephthalate, and nylon can be used.

  EXAMPLES Hereinafter, although an experimental example, an Example, and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, the blending amount is mass%.

[Experimental example]
A dentifrice composition (toothpaste) having the composition shown in Table 1 was prepared by the following method and evaluated as follows. The results are shown in Table 1.

(1) Preparation of test dentifrice composition A dentifrice composition having the composition shown in Table 1 was prepared by a conventional method, and the innermost layer was a linear low density polyethylene 26 mm diameter and 8 mm diameter laminated tube (low density polyethylene). 72 μm / ethylene / acrylic acid copolymer resin 90 μm / aluminum 10 μm / ethylene / acrylic acid copolymer resin 35 μm / linear low density polyethylene 50 μm, thickness 257 μm (manufactured by Dai Nippon Printing Co., Ltd.) was filled with 50 g. .

For preparation of the dentifrice composition, hinokitiol (Takasago Fragrance Co., Ltd.), disodium edetate (disolvin NA2, Lion Co., Ltd., trisodium edetate (Zonon T, Daiichi Chemicals Co., Ltd.), edetic acid Dipotassium dihydrate (Kyrest 2K-SD (Chillest Co., Ltd.)), Edetate tetrasodium dihydrate (Zonon N, Daiichi Chemicals Co., Ltd.), Ethanol (Japan Alcohol Sales Co., Ltd.), Sodium Polyphosphate (Taihei Chemical Industry Co., Ltd.) For the other components, standard products of quasi-drug raw material standards were used.
In addition, about the fragrance | flavor, the fragrance | flavor A-the fragrance | flavor D shown in Table 2 were created and mix | blended.

(I) Evaluation method of antibacterial activity test Each 40 μL of the Porphyromonas gingivalis culture solution that has been cryopreserved contains 5 mg / L hemin (Sigma) and 1 mg / L vitamin K (Wako Pure Chemical Industries). Todd Hewit broth (manufactured by Becton and Dickinson) was added to 4 mL of a culture solution (THBHM), and anaerobic culture was performed at 37 ° C. overnight (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen) to obtain a bacterial solution. After adding 49 mL of THBHM medium to 1 g of the prepared dentifrice composition and stirring, THBHM medium was further added to prepare each dentifrice diluted medium so that the dentifrice dilution ratio was 400 to 2400 times. 50 μL of the bacterial solution was added to 3 mL of each toothpaste diluted medium, and after anaerobic culture at 37 ° C. for 10 days, the presence or absence of the growth of the bacteria was determined by appearance, smell, and microscope. The antibacterial activity was shown as the maximum dilution at which no bacterial growth was observed.

(Ii) Method for evaluating discoloration After the dentifrice composition was stored at 60 ° C. for 1 month, 5 cm was put out on the paper and visually evaluated according to the following criteria.
Evaluation criteria;
◎: No discoloration ○: Almost no discoloration △: Some discoloration ×: Discoloration

(Iii) Evaluation Method for Liquid Separation The dentifrice composition was stored at 60 ° C. for 1 month, then put out 5 cm on a sheet of paper, and visually evaluated according to the following criteria.
Evaluation criteria;
◎: No liquid separation ○: Little liquid separation (less than 1 mm)
Δ: Some liquid separation (1 mm or more and less than 5 mm)
X: There is liquid separation (5 mm or more)

＊：組成中に含有する水分量の合計（以下、同様）。

*: Total amount of water contained in the composition (hereinafter the same).

＊表中、部はいずれも質量部である（以下、同様。）。

* In the table, all parts are parts by mass (the same applies hereinafter).

  From the results shown in Table 1, in the case where any of hinokitiol, edetate, ethanol, and water is not included in the composition, or the composition (comparative example) in which the blending amount and blending ratio of these components are inappropriate, the antibacterial activity is inferior. Causes discoloration and phase-liquid separation, resulting in poor storage stability. In contrast, by combining hinokitiol, edetate, ethanol and water in combination at an appropriate blending amount and blending ratio (Example), antibacterial activity derived from hinokitiol is enhanced, and an excellent antibacterial action is exhibited. In addition, it was confirmed that there was almost no discoloration or phase-liquid separation after long-term storage, and the storage stability was excellent.

  Next, the composition for oral cavity having the following composition was prepared and evaluated in the same manner. All of them have high antibacterial activity, no discoloration with time, and excellent phase-liquid separation stability. confirmed.

[Example 16] Toothpaste Hinokitiol 0.01%
Edetate disodium 0.2
Ethanol 0.5
Isopropylmethylphenol 0.1
Lauroyl sarcosine sodium 0.2
Tocopherol acetate 0.1
Sodium lauryl sulfate 1.0
Fragrance A 1.0
Carrot extract 0.001
Rosemary extract 0.001
Sage extract 0.001
Polyoxyethylene (20) hydrogenated castor oil 1.8
Silicic anhydride 20
Sodium polyacrylate 0.3
Xanthan gum 0.8
Sorbit liquid (70%) 35
Saccharin sodium 0.2
Propylene glycol 3.0
Methyl paraoxybenzoate 0.05
Butyl paraoxybenzoate 0.01
Titanium oxide 0.4
Sodium fluoride 0.21
Water 35.017
Total 100.0%
Water / ethanol mass ratio: 67.3

[Example 17] Toothpaste hinokitiol 0.01%
Edetate disodium 0.2
Ethanol 0.2
Oat extract 0.05
β-glycyrrhetinic acid 0.05
Tocopherol acetate 0.1
Sodium lauryl sulfate 1.0
Fragrance A 1.0
Carrot extract 0.001
Rosemary extract 0.001
Sage extract 0.1
Chamomile extract 0.001
Ogon Extract 0.1
Polyoxyethylene (20) hydrogenated castor oil 1.0
Polyoxyethylene stearyl ether 1.0
Silicic anhydride 5.0
Calcium carbonate 20
Sodium polyacrylate 0.3
Sodium carboxymethylcellulose 1.0
Sorbit liquid (70%) 40
Saccharin sodium 0.2
Propylene glycol 3.0
Benzalkonium chloride 0.01
Sodium monofluorophosphate 0.73
Water 24.947
Total 100.0%
Water / ethanol mass ratio: 113.4

Claims (2)

(A) 0.005-0.2 mass% of hinokitiol,
(B) edetate disodium, edetate trisodium, edetate dipotassium dihydrate, at least one of edetate selected from edetate tetrasodium dihydrate 0.1-0.5 wt%,
(C) 0.2 to 3% by mass of ethanol,
(D) is water 30-45 wt%
A toothpaste composition comprising (d) / (c) in a mass ratio of 70 to 150.   The toothpaste composition according to claim 1, which does not contain allantoins.