Oral components

Abstract

To provide an oral composition with excellent retention properties for antibacterial components. [Solution] Contains cetylpyridinium chloride and benzalkonium chloride, The benzalkonium chloride mentioned above includes benzalkonium chloride having a C14 linear alkyl group, The ratio of the mass content of benzalkonium chloride having a C12 linear alkyl group to the mass content of benzalkonium chloride having a C14 linear alkyl group is 7:3 to 0:10. Oral composition.

Description

Technical Field

[0001] The present disclosure relates to oral compositions and the like. The contents of all documents described in this specification are incorporated herein by reference.

Background Art

[0002] In many oral compositions, a bactericidal component is incorporated in anticipation of a bactericidal effect.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0004] However, if the bactericidal component is washed away by the influence of saliva or the like when applied in the oral cavity, its efficacy will deteriorate. Therefore, it is preferable that the bactericidal component incorporated in the oral composition has good retention.

Means for Solving the Problems

[0005] The present inventors have attempted to develop a method for improving the retention of a bactericide incorporated in an oral composition in the oral cavity (particularly on the tooth surface), found that the problem can be solved by combining specific bactericides, and further refined them.

[0006] The present disclosure includes, for example, the subject matters described in the following items. Item 1. Containing cetylpyridinium chloride and benzalkonium chloride, wherein the benzalkonium chloride has the formula:

[0007] [ka] It contains benzalkonium chloride having a C14 linear alkyl group, represented as: formula:

[0008] [ka] The mass of benzalkonium chloride having a C12 linear alkyl group, represented by The ratio of the content mass to the benzalkonium chloride having the C14 linear alkyl group is, It is 7:3 to 0:10. Oral composition. Section 2. The oral composition according to item 1, containing 0.001 to 0.1% by mass of benzalkonium chloride. Section 3. An oral composition according to item 1 or 2, containing 0.01 to 0.5% by mass of cetylpyridinium chloride. [Effects of the Invention]

[0009] The present invention provides a bactericidal component that exhibits excellent retention in the oral cavity (especially on the tooth surface), and an oral composition containing the bactericidal component. [Modes for carrying out the invention]

[0010] The embodiments included in this disclosure will be described in more detail below. This disclosure preferably includes, but is not limited to, specific combinations of bactericides and oral compositions containing such combinations of bactericides, and includes everything disclosed herein and recognizable to those skilled in the art.

[0011] The oral compositions included in this disclosure contain cetylpyridinium chloride and benzalkonium chloride. These oral compositions may be referred to as the oral compositions of this disclosure.

[0012] Cetylpyridinium chloride is a compound represented by the following formula. In this specification, cetylpyridinium chloride may be referred to as CPC.

[0013] [Chemical formula] CPC is preferably contained in the oral composition of the present disclosure at, for example, 0.01 to 0.5% by mass. The upper or lower limit of this range may be, for example, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, or 0.45% by mass. For example, this range may be 0.02 to 0.1% by mass.

[0014] Benzalkonium chloride has the following formula:

[0015] [Chemical formula] (In the formula, R represents a C8-C18 linear alkyl group) and is a compound represented by this. In this specification, benzalkonium chloride may be referred to as BKC.

[0016] Benzalkonium chloride is particularly such that R in the formula is a C8 linear alkyl group (-(CH2)7CH3), a C10 linear alkyl group (-(CH2)9CH3), a C12 linear alkyl group (-(CH2) 11 CH3), a C14 linear alkyl group (-(CH2) 13 CH3), a C16 linear alkyl group (-(CH2) 15 CH3), or a C18 linear alkyl group (-(CH2) 17 CH3), and compounds thereof are preferred, or mixtures of two or more selected from the group consisting of these compounds are also preferred. Among them, R in the formula is a C12 linear alkyl group (-(CH2) 11 CH3), a C14 linear alkyl group (-(CH2) 13 CH3), or a C16 linear alkyl group (-(CH2) 15Compounds that are CH3 are preferred, or a mixture of two or more compounds selected from the group consisting of these compounds is also preferred.

[0017] In this specification, compounds in which R represents a C12 linear alkyl group are sometimes referred to as BKC12, compounds in which R represents a C14 linear alkyl group are sometimes referred to as BKC14, and compounds in which R represents a C16 linear alkyl group are sometimes referred to as BKC16.

[0018] The oral composition of this disclosure preferably contains at least BKC14, and more preferably 30% by mass or more of BKC is BKC14. It is also preferable that it contains both BKC14 and BKC12.

[0019] Furthermore, it is preferable that the ratio of the mass of BKC12 contained to the mass of BKC14 contained (BKC12:BKC14) is 7:3 to 0:10. A ratio of 0:10 means that BKC12 is not contained in the oral composition of this disclosure. This ratio may be, for example, 6.5:3.5 to 0:10, 6:4 to 0:10, 5.5:4.5 to 0:10, or 5:5 to 0:10. Also, if BKC14 and BKC12 are contained in the oral composition of this disclosure, the mass ratio (BKC12:BKC14) may be, for example, about 1:0.3 to 100. The upper or lower limits of the range (1 to 100) are, for example, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45 , 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99. For example, the range may be 0.4 to 50.

[0020] BKC is preferably contained in the oral composition of this disclosure in an amount of, for example, 0.001 to 0.1% by mass. The upper or lower limit of this range may be, for example, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.015, 0.02, 0.025, 0.03, 0.035, 0.04, or 0.045, 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, or 0.095% by mass. For example, this range may be 0.005 to 0.05% by mass.

[0021] The oral compositions of this disclosure may be solid compositions or liquid compositions. These oral compositions can be used, for example, as pharmaceuticals or quasi-drugs. The forms of the oral compositions of this disclosure are not particularly limited, but can be made into forms (dosage forms) such as ointments, pastes, pastes, gels, liquids, sprays, mouthwashes, liquid toothpastes, toothpastes, and gums according to conventional methods. Among these, mouthwashes, liquid toothpastes, toothpastes, ointments, pastes, liquids, and gels are preferred.

[0022] The oral compositions of this disclosure may contain, alone or in addition to two or more optional components that can be incorporated into oral compositions, as long as they do not impair the effects.

[0023] For example, surfactants include nonionic surfactants, anionic surfactants, or amphoteric surfactants. Surfactants can be added. Specifically, examples of nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters, maltose fatty acid esters, and lactose fatty acid esters; fatty acid alkanolamides; sorbitan fatty acid esters; fatty acid monoglycerides; polyoxyethylene alkyl ethers with a polyoxyethylene addition coefficient of 8 to 10 and 13 to 15 carbon atoms in the alkyl group; polyoxyethylene alkylphenyl ethers with a polyoxyethylene addition coefficient of 10 to 18 and 9 carbon atoms in the alkyl group; diethyl sebacate; polyoxyethylene hydrogenated castor oil; and fatty acid polyoxyethylene sorbitan. Examples of anionic surfactants include sulfate ester salts such as sodium lauryl sulfate and sodium polyoxyethylene lauryl ether sulfate; sulfosuccinates such as sodium lauryl sulfosuccinate and sodium polyoxyethylene lauryl ether sulfosuccinate; acyl amino acid salts such as sodium cocoyl sarcosinate and sodium lauroyl methylalanine; and sodium cocoyl methyl taurate. Examples of amphoteric surfactants include betaine-type surfactants such as lauryldimethylaminoacetic acid betaine and coconut oil fatty acid amidopropyldimethylaminoacetic acid betaine; imidazoline-type surfactants such as N-cocoyl-N-carboxymethyl-N-hydroxyethylethylenediamine sodium; and amino acid-type surfactants such as N-lauryldiaminoethylglycine. These surfactants can be used individually or in combination of two or more. The amount used is usually 0.1 to 5% by mass of the total composition.

[0024] Furthermore, as flavoring agents, for example, menthol, carboxylic acid, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellol, α-terpineol, methyl acetate, citronenyl acetate, methyl eugenol, cineole, linalool, ethyl linalool, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, perilla oil, wintergreen oil, clove oil, eucalyptus oil, pimento oil, d-camphor, d-borneol, fennel oil, cinnamon oil, cinnamaldehyde, peppermint oil, vanillin, and other fragrances can be used. These can be used individually or in combination of two or more, in amounts of, for example, 0.001 to 1.5% by mass of the total composition. It can be combined.

[0025] Furthermore, sweeteners such as sodium saccharin, potassium acesulfamethamate, stevioside, neohesperidyl dihydrochalcone, perillartin, thaumatin, aspartylphenylalanyl methyl ester, and p-methoxycinnamic aldehyde can be used. These should be added in an amount of, for example, 0.01 to 1% by mass relative to the total amount of the composition. It is possible.

[0026] Furthermore, sorbitol, ethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, polypropylene glycol, xylitol, maltitol, lactitol, polyoxyethylene glycol, etc., can be used as humectants, either individually or in combination of two or more.

[0027] As binders, cellulose derivatives such as sodium carboxymethylcellulose, carboxymethyl ethylcellulose salt, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, ethylcellulose, crystalline cellulose, crystalline cellulose / carmellose sodium, microbially produced polymers such as xanthan gum, natural polymers or natural rubbers such as tragacanth gum, karaya gum, arabic gum, carrageenan, dextrin, agar, pectin, pullulan, gellan gum, locust bean gum, and sodium alginate, synthetic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, polyvinyl methyl ether, and sodium polyacrylate, inorganic binders such as thickening silica and bee gum, and carboxymethylcellulose such as O-[2-hydroxy-3-(trimethylammonio)propyl]hydroxyethylcellulose chloride. Thionic binders are one example. These binders can be used individually or in combination of two or more.

[0028] As preservatives, parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, sodium benzoate, phenoxyethanol, and alkyldiaminoethylglycine hydrochloride may be included.

[0029] As coloring agents, legally approved pigments such as Blue No. 1, Yellow No. 4, Red No. 202, and Green No. 3, mineral pigments such as ultramarine, enhanced ultramarine, and navy blue, and titanium dioxide may be added.

[0030] As pH adjusters, citric acid, phosphoric acid, malic acid, pyrophosphate, lactic acid, tartaric acid, glycerophosphate, acetic acid, nitric acid, or chemically possible salts thereof, or sodium hydroxide may be included. These can be included individually or in combination of two or more so that the pH of the composition is in the range of 4 to 8, preferably 5 to 7. The amount of pH adjuster may be, for example, 0.01 to 2% by weight.

[0031] The oral compositions disclosed herein may also use pharmaceutically active ingredients other than CPC and BKC. For example, vitamin E derivatives such as dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate; amphoteric bactericides such as dodecyldiaminoethylglycine; nonionic bactericides such as triclosan, isopropylmethylphenol, and hinokitiol; anionic bactericides such as sodium lauroyl sarcosinate; cationic bactericides such as chlorhexidine hydrochloride and benzethonium chloride; enzymes such as dextranase, amylase, protease, mutanase, lysozyme, and lytic enzymes (Litec enzyme); sodium monofluorophosphate, etc. Alkali metal monofluorophosphates such as potassium nofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, tranexamic acid, epsilon-aminocaproic acid, aluminum chlorohydroxyl allantoin, dihydrocholesterol, glycyrrhetinic acid, glycyrrhizic acid, sodium copper chlorophyllin, glycerophosphate, chlorophyll, sodium chloride, caropeptide, allantoin, carbazochrome, hinokitiol, potassium nitrate, and palatinite can be formulated individually or in combination of two or more.

[0032] Furthermore, it is possible to add alcohols, silicones, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, Plastibase, etc., as base materials.

[0033] Furthermore, the oral compositions of this disclosure can be prepared by known methods or by methods readily conceivable from known methods. For example, they can be prepared by appropriately mixing CPC and BKC and other components as needed.

[0034] The oral compositions of this disclosure are not particularly limited in their application to humans and non-human mammals. Preferred non-human mammals include livestock and pets, and more specifically, dogs, cats, mice, rats, horses, cattle, sheep, monkeys, and the like.

[0035] In this specification, the term "comprising" includes both "consisting essentially of" and "consisting of." Furthermore, this disclosure encompasses all any combination of the constituent elements described herein.

[0036] Furthermore, the various characteristics (properties, structure, function, etc.) described for each embodiment of this disclosure described above may be combined in any way to identify the subject matter covered by this disclosure. In other words, this disclosure encompasses all subject matter consisting of any combination of each of the combinatable properties described herein. [Examples]

[0037] The embodiments of this disclosure will be described in more detail below with examples, but the embodiments of this disclosure are not limited to the examples below.

[0038] [Collection of saliva] Saliva collection was performed in a cleanroom. Saliva was collected from subjects until approximately 3 ml of naturally secreted saliva was collected. The collected saliva was processed using a swing-rotor centrifuge at 5°C, 11,000 rpm, and for 10 minutes, and the supernatant fraction was collected. The collected supernatant fraction was irradiated with ultraviolet light under ice for approximately 1 hour and refrigerated until ready for testing.

[0039] [Preparation of HAP (hydroxyapatite) support] A HAP carrier (hydroxyapatite powder treated with saliva) exhibiting similar behavior to that of a tooth surface was prepared according to the following procedure.

[0040] 50 mg of hydroxyapatite powder (Bio-Gel HTP Gel; manufactured by BIO-RAD Lab.) was weighed into a PP tube (Falcon2059), 2 ml of distilled water was added, and the mixture was shaken for 1 hour. After the treatment, the mixture was centrifuged at room temperature, 3000 rm, and 5 minutes, and the supernatant was removed. Next, 2 ml of the saliva obtained above was added, homogenized with a touch mixer, and then shaken in a constant temperature chamber set at 37°C for approximately 15 hours. After that, the mixture was centrifuged again at room temperature, 3000 rm, and 5 minutes, and the supernatant was removed to obtain the "HAP carrier".

[0041] [Adsorption test] 2 ml of each sample was added to the HAP carrier (approximately 50 mg) obtained above, and after homogenization using a touch mixer, the mixture was shaken for 15 minutes in a constant temperature chamber set to 37°C. The supernatant was removed by centrifugation at room temperature, 3000 rm, and 5 minutes. 2 ml of distilled water was added to the obtained residue, and after homogenization using a touch mixer, the supernatant was removed by centrifugation at room temperature, 3000 rm, and 5 minutes. The obtained residue was washed with distilled water under the same conditions as above to obtain the HAP carrier after adsorption treatment as the residue.

[0042] [Measurement of adsorption amount] The pH of 1000 ml of distilled water containing 4.2 g of citric acid and 4.64 g of monosodium dihydrogen citrate was adjusted to 3.0. Next, 2.88 g of sodium lauryl sulfate was added, followed by 3000 ml of acetonitrile, which was mixed to form a homogenized solution. After degassing, this solution was used as the extraction solvent. 5 ml of the extraction solvent was added to the HAP carrier obtained after the adsorption treatment, mixed to form a homogenized solution using a touch mixer, and then shaken for 10 minutes. After the treatment, the solution was centrifuged at room temperature at 3000 rpm for 5 minutes, and the resulting supernatant was collected in a 20 ml volumetric flask. The extraction treatment was repeated, and the resulting supernatant was weighed into the volumetric flask. The solution was then diluted to 20 ml, and the cetylpyridinium chloride and benzalkonium chloride content in the resulting solution was measured using HPLC. Specifically, standard solutions of known concentrations of cetylpyridinium chloride and each benzalkonium chloride were prepared, and the adsorption amount was calculated by comparing the peak area with that of the retention test sample. The HPLC analysis conditions were as follows: <Analysis conditions> Column: C18 column (reverse phase) Mobile phase: Perchloric acid solution / acetonitrile mixture Temperature: 50℃ Detector: PDA (around 250-260 nm) The results were obtained by calculating the amount of cetylpyridinium salt adsorbed (μg) and benzalkonium chloride adsorbed (μg) per 50 mg of HAP carrier.

[0043] [Subject] Formulations 1 and 2-1 to 2-5, which can be used as oral compositions, were prepared according to the compositions shown in Table 1. The values ​​of each component listed in Table 1 are in grams (g). Formulation 1 does not contain BKC. Formulations 2-1 to 2-5 all contain 0.01g of BKC, but the amounts of BKC12 and BKC14 contained in the BKC differ. The breakdown of BKC used in Formulations 2-1 to 2-5 is shown in Table 2. [Table 1] [Table 2]

[0044] The adsorption properties (i.e., retention on the tooth surface) of formulations 1 and 2-1 to 2-5 to HAP were examined, and the results are shown in Table 3, in terms of the amount of CPC (μg) and BKC (μg) adsorbed on HPA. [Table 3] The following table shows examples of prescriptions. Note that the unit of the ingredient amounts in each prescription example is mass percent.

[0045] Prescription examples (liquid or gel formulations) [Table 4]

[0046] Prescription example (toothpaste) [Table 5]

Claims

1. It contains (α) cetylpyridinium chloride and (β) benzalkonium chloride, The (β) benzalkonium chloride mentioned above is given by formula: 【Chemistry 1】 It contains benzalkonium chloride having a C14 linear alkyl group, represented as: formula: 【Chemistry 2】 The mass of benzalkonium chloride having a C12 linear alkyl group, represented by the above, The ratio of the content mass to the benzalkonium chloride having the C14 linear alkyl group is, The ratio is 3:7 to 0:

10. The (β) benzalkonium chloride is benzalkonium chloride having a C14 linear alkyl group in an amount of 70% by mass or more. Oral composition.

2. The oral composition according to claim 1, comprising 0.001 to 0.1% by mass of (β)benzalkonium chloride.

3. The oral composition according to claim 1 or 2, comprising 0.01 to 0.5% by mass of (α) cetylpyridinium chloride.

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