Oral components

Abstract

To provide an oral composition that prevents the sterilizing power of dodecylpyridinium chloride from decreasing due to saliva.SOLUTION: An oral composition comprises dodecylpyridinium chloride and a monosaccharide and / or a monosaccharide alcohol.SELECTED DRAWING: None

Description

Technical Field

[0001] The present disclosure relates to oral compositions and the like, and more particularly to oral compositions and the like containing a specific bactericide (dodecylpyridinium chloride). The contents of all documents described in this specification are incorporated herein by reference.

Background Art

[0002] It is known that quaternary ammonium compounds (especially quaternary ammonium salts) may be used as bactericides.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0004] Among quaternary ammonium salts, cetylpyridinium chloride (also denoted as "CPC") is a bactericide widely used in oral compositions and the like, but its bactericidal activity may be reduced by saliva. Also, it has been found that not only CPC but quaternary ammonium salts in general may have their bactericidal activity reduced when in contact with saliva.

[0005] Therefore, there has been a demand for an oral composition containing a bactericide (especially a quaternary ammonium salt) that can be suitably applied in the oral cavity and in which the reduction in the bactericidal activity of the bactericide due to saliva during oral application is suppressed.

Means for Solving the Problems

[0006] As a result of their extensive research, the inventors discovered that among quaternary ammonium salts, oral compositions containing dodecylpyridinium chloride (also referred to as "DPC") together with a monosaccharide or monosaccharide alcohol suppress the reduction of DPC's bactericidal activity due to saliva, and further improvements were made based on this discovery.

[0007] This disclosure includes, for example, the following subjects: Section 1. (A) Dodecylpyridinium chloride, and (B) At least one selected from the group consisting of monosaccharides and monosaccharide alcohols An oral composition containing [the specified ingredient]. Section 2. (B) At least one selected from the group consisting of monosaccharides and monosaccharide alcohols, At least one selected from the group consisting of aldopentoses and aldohexoses, and monosaccharide alcohols having a structure in which the aldehyde group of these monosaccharides is replaced with a hydroxyl group. The oral composition described in item 1. Section 3. (B) At least one selected from the group consisting of monosaccharides and monosaccharide alcohols, It is at least one selected from the group consisting of xylose, arabinose, ribose, glucose, mannose, fructose, and sorbitol. The oral composition described in item 2. Section 4. (A) Dodecylpyridinium chloride, and (B) Xylose An oral composition containing [the specified ingredient]. Section 5. (A) contains 0.05 to 250 parts by mass of (B) per 1 part by mass of (A), An oral composition as described in any of items 1 to 4. Section 6. An oral composition according to any one of items 1 to 5, containing 0.01 to 0.3% by mass of (A). [Effects of the Invention]

[0008] A DPC-containing oral composition is provided in which the reduction of DPC's bactericidal activity due to saliva is suppressed. [Modes for carrying out the invention]

[0009] The embodiments included in this disclosure will be described in further detail below. This disclosure preferably includes, but is not limited to, oral compositions, and encompasses everything disclosed herein and recognizable to those skilled in the art.

[0010] The oral compositions included in this disclosure contain DPC and monosaccharides and / or monosaccharide alcohols. Hereinafter, the oral compositions included in this disclosure may be referred to as "the oral compositions of this disclosure."

[0011] Preferred monosaccharides include pentoses and hexoses. Aldoses are also preferred. Aldopentoses and aldoxyses are more preferred. As monosaccharide alcohols, sugar alcohols of the above monosaccharides are preferred, and those having a structure in which the aldehyde group of the aldose is replaced with a hydroxyl group are more preferred. More specifically, preferred monosaccharides include xylose, arabinose, ribose, glucose, mannose, and fructose. More specifically, preferred monosaccharide alcohols include sorbitol and mannitol. Both D-isomers and L-isomers can be used. Preferably, the L-isomer of arabinose is used, and the D-isomers of the others are used.

[0012] Monosaccharides and monosaccharide alcohols can be used individually or in combination of two or more. The monosaccharides and / or monosaccharide alcohols contained in the oral compositions of this disclosure may be referred to as "(B) component".

[0013] In the oral composition of this disclosure, preferably, the specific sugar is contained in an amount of about 0.05 to 250 parts by mass per 1 part by mass of DPC.The upper or lower limits of the range are, for example, 0.1, 0.2, 0.3, 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, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 19 It may also be 3, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, or 249 parts by mass. For example, the range may be 0.1 to 200 parts by mass.

[0014] In the oral compositions of this disclosure, DPC is preferably contained in an amount of about 0.01 to 0.3% 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, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, or 0.29% by mass. For example, the range may be 0.02 to 0.09% by mass.

[0015] In the oral compositions of this disclosure, component (B) is preferably contained in an amount of about 0.005 to 50% by mass. The upper or lower limits of this range are, for example, 0.01, 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, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.05, and 1.1. , 1.15, 1.2, 1.25, 1.3, 1.35, 1.4, 1.45, 1.5, 1.55, 1.6, 1.65, 1.7, 1.75, 1.8, 1.85, 1.9, 1.95, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, 20, 20.5, 21, 21.5, 22, 22.5, 23, 23.5, 24, 24.5, 25, 25.5, 26, 26.5, 27, 27.5, 28, 28.5, 29, 29.5, 30, 30.5, 31, 31.5, 32, The mass percentage may be 32.5, 33, 33.5, 34, 34.5, 35, 35.5, 36, 36.5, 37, 37.5, 38, 38.5, 39, 39.5, 40, 40.5, 41, 41.5, 42, 42.5, 43, 43.5, 44, 44.5, 45, 45.5, 46, 46.5, 47, 47.5, 48, 48.5, 49, or 49.5%. For example, the range may be 0.01 to 20% by mass.

[0016] In addition, the oral composition of the present disclosure preferably has a pH of 4 to 9. The upper or lower limit of the pH range may be, for example, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, or 8.9. For example, the pH range may be 5 to 8.

[0017] The oral composition of the present disclosure can be produced by a known method or a method easily conceived from a known method. In addition, the oral composition of the present disclosure can also be used, for example, as a pharmaceutical product, quasi-drug, or cosmetic. The form of the oral composition of the present disclosure is not particularly limited, but can be, for example, in the form (dosage form) of an ointment, paste, pasta, gel, liquid, spray, mouthwash, liquid dentifrice, toothpaste, coating agent, etc.

[0018] In addition to DPC and component (B), in the oral composition of the present disclosure, optional components that can be formulated in the oral composition may be further formulated alone or in combination of two or more, as long as the effects of the present invention are not impaired.

[0019] For example, nonionic surfactants, anionic surfactants, or amphoteric surfactants can be incorporated as surfactants. 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; fatty acid polyoxyethylene sorbitan; alkyl glucosides with 8 to 16 carbon atoms in the alkyl group, etc. 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 activators such as lauryl dimethylaminoacetic acid betaine and coconut oil fatty acid amidopropyl dimethylaminoacetic acid betaine; imidazoline-type activators such as N-cocoyl-N-carboxymethyl-N-hydroxyethylethylenediamine sodium; and amino acid-type activators such as N-lauryl diaminoethylglycine. In addition, coconut oil fatty acid monoethanolamide, coconut oil fatty acid diethanolamide, coconut oil fatty acid amide betaine, coconut oil fatty acid amidopropyl betaine, and N-coconut oil fatty acid acyl L-arginine ethyl dl-pyrrolidone carboxylate are also preferred examples. These surfactants can be formulated individually or in combination of two or more. The amount of this ingredient is typically, for example, 0.1 to 5% by mass of the total amount of the composition.

[0020] Furthermore, sweeteners such as sodium saccharin, acesulfame potassium, stevioside, sucralose, neohesperidyl dihydrochalcone, perillartin, thaumatin, aspartylphenylalanyl methyl ester, and p-methoxycinnamic aldehyde may be included. These can be used individually or in combination of two or more. They can also be included in amounts of, for example, 0.01 to 1% by mass relative to the total amount of the composition.

[0021] Furthermore, as binders, one or more of the following can be used in combination: cellulose derivatives such as sodium carboxymethylcellulose, carboxymethyl ethylcellulose salt, hydroxyethylcellulose, hydroxypropylcellulose, and hydroxypropyl methylcellulose; microbially produced polymers such as xanthan gum and gellan gum; natural polymers or natural rubbers such as tragacanth gum, karaya gum, arabic gum, carrageenan, and dextrin; synthetic polymers such as polyvinyl alcohol and polyvinylpyrrolidone; inorganic binders such as thickening silica and bee gum; and cationic binders such as O-[2-hydroxy-3-(trimethylammonio)propyl]hydroxyethylcellulose chloride.

[0022] Furthermore, humectants such as sorbitol, glycerin, propylene glycol, xylitol, maltitol, lactitol, and polyoxyethylene glycol can be included individually or in combination of two or more.

[0023] As preservatives, parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, sodium benzoate, phenoxyethanol, and alkyldiaminoethylglycine hydrochloride may be included individually or in combination of two or more.

[0024] 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 blended individually or in combination of two or more.

[0025] 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, for example, 4 to 9, preferably 5 to 8. The amount of pH adjuster included is exemplified by 0.01 to 2% by weight.

[0026] Other fungicides besides dodecylpyridinium chloride may be included as active ingredients. Examples include cationic fungicides such as cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, and chlorhexidine gluconate; amphoteric fungicides such as dodecyldiaminoethylglycine; nonionic fungicides such as triclosan and isopropylmethylphenol; and hinokitiol. Furthermore, other active ingredients besides fungicides may also be included. For example, vitamin E derivatives such as aluminum lactate, potassium nitrate, dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate, and sodium fluoride may be included. Active ingredients may be included individually or in combination of two or more.

[0027] Furthermore, it is possible to add base materials such as alcohols, silicones, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, and Plastibase, either individually or in combination of two or more.

[0028] Please note that the above list of optional components is for illustrative purposes only and does not limit the optional components that may be used.

[0029] Because the oral composition of this disclosure contains the aforementioned specific monosaccharide and / or monosaccharide alcohol, the reduction in the bactericidal activity of DPC by saliva is suppressed. Therefore, the time required for sterilization is shorter compared to cases where the aforementioned specific sugar is not contained. Thus, it becomes possible to shorten the time required for oral care. Furthermore, the bactericidal activity of DPC can be preferably used in the oral composition for sterilizing periodontal disease bacteria, for example. For this reason, although not particularly limited, the oral composition of this disclosure can also be preferably used for subjects who carry oral periodontal disease bacteria (especially patients with periodontal disease). Moreover, since the reduction in the bactericidal activity of DPC by saliva varies from person to person (for example, some people experience a significant reduction in the bactericidal activity of DPC by saliva, while others experience a milder reduction), the oral composition of this disclosure can also be preferably used for subjects for whom suppression of the reduction in the bactericidal activity of DPC by saliva is required (more specifically, for example, subjects whose bactericidal activity of DPC is reduced by saliva, subjects suffering from oral diseases caused by bacteria such as periodontal disease, etc.). Furthermore, the scope includes not only humans but also non-human mammals. For example, pets and livestock may also be included. More specifically, dogs, cats, monkeys, cows, horses, pigs, sheep, goats, mice, rats, etc., may also be included.

[0030] This disclosure also includes a method for suppressing the reduction of DPC bactericidal activity by saliva, which involves using DPC in combination with the specified sugar, and a method for producing an oral composition, which involves incorporating DPC and the specified sugar into the composition.

[0031] 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.

[0032] Furthermore, the various characteristics (properties, structure, function, etc.) described in each embodiment of this disclosure above may be combined in any way to identify the subject matter covered by this disclosure. In other words, this disclosure covers all subject matter consisting of any combination of the combinable characteristics described herein. [Examples]

[0033] 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.

[0034] Saliva collection Each subject (Subjects A-D) was asked to brush their teeth with toothpaste that did not contain surfactants or disinfectants, and 10 mL of saliva (non-irritating saliva) was collected from each subject. The collected saliva was stored in the refrigerator, and immediately before use, it was aspirated and dispensed five times using a 23G needle and a 10 mL syringe (both manufactured by Terumo Corporation) before being used.

[0035] Preparation of the test drug solution Aqueous solutions of the test drug were prepared containing 0.05% (w / v) dodecylpyridinium chloride (DPC) and 0.01%, 0.1%, 0.5%, 1%, or 10% (w / v) of each sugar (see Table 1).

[0036] Note that the concentration of each test drug aqueous solution is shown in %(w / v), but since this is almost the same as the %(w / w) value (the %(w / w) value is only slightly larger), it is acceptable to interpret it as %(w / w) (i.e., mass%).

[0037] Sterilization test 1 200 μL of the test drug aqueous solution was dispensed into column A of a 96-well plate, and 200 μL of TSB medium for DPC inactivation and oral bacterial culture was dispensed into columns B through H.

[0038] Furthermore, since TSB medium can inactivate DPC, the sterilization time can be adjusted by adjusting the timing of its addition. The TSB medium used was prepared by dissolving 30g of Tripticase Soy Broth (TSB), 1g of Yeast Extract, 1g of Hemin / menadion solution, 0.7g of lecithin, and 5g of Tween80 in distilled water, making up to 1L, and then autoclaving the mixture. The Hemin / menadion solution was prepared by dissolving 0.25g of Hemin in 5ml of 1N NaOH, adding 20ml of distilled water, and then mixing in 0.025g of menadion (Vitamin K3) dissolved in 25ml of 99% ethanol.

[0039] 20 μL of saliva was added to column A, pipettered, and then 20 μL each was added from column A to columns B through H at each time interval. More specifically, the measurement started when 20 μL of saliva was added to column A and mixed by pipetting. 20 μL of the solution from column A was then added to column B after 30 seconds, to column C after 60 seconds, to column D after 90 seconds, to column E after 120 seconds, to column F after 180 seconds, to column G after 240 seconds, and to column H after 300 seconds, and mixed by pipetting. After that, anaerobic culture was performed for 48 hours, and the presence or absence of bacterial growth was visually confirmed to determine whether the bacteria were alive or dead. More specifically, if the culture medium was turbid visually, it was determined that bacteria had proliferated and that the bacteria in the solution had not been completely killed.

[0040] Each solution sampled from column A was evaluated after 30, 60, 90, 120, 180, 240, and 300 seconds. The time at which the culture medium was no longer cloudy and the bacteria in the solution were killed was defined as the sterilization time.

[0041] Table 1 shows the relative sterilization times when each monosaccharide or monosaccharide alcohol is added, with the sterilization time of each subject's saliva using 0.05% (w / v) dodecylpyridinium chloride alone set to 100%. For example, if the sterilization time when 0.05% (w / v) dodecylpyridinium chloride was mixed with subject A's saliva was 120 seconds, and the sterilization time when an aqueous solution of the test drug containing 0.05% (w / v) dodecylpyridinium chloride and 0.5% (w / v) sugar was mixed with subject A's saliva was 60 seconds, then the relative sterilization time in this case is 50%. Note that blank spaces in the relative sterilization time value indicate that the study was not conducted.

[0042] [Table 1]

[0043] The following are examples of prescriptions. Note that the values ​​for each component listed in the table below represent mass percentages.

[0044] <Liquid and gel formulations>

[0045] [Table 2]

[0046] <Toothpaste>

[0047] [Table 3]

Claims

1. (A) Dodecylpyridinium chloride, and (B) At least one selected from the group consisting of monosaccharides and monosaccharide alcohols It contains, (A) contains 0.01 to 0.05% by mass, Oral composition.

2. (B) At least one selected from the group consisting of monosaccharides and monosaccharide alcohols, At least one selected from the group consisting of aldopentoses and aldohexoses, and monosaccharide alcohols having a structure in which the aldehyde group of these monosaccharides is replaced with a hydroxyl group. The oral composition according to claim 1.

3. (B) At least one selected from the group consisting of monosaccharides and monosaccharide alcohols, It is at least one selected from the group consisting of xylose, arabinose, ribose, glucose, mannose, fructose, and sorbitol. The oral composition according to claim 2.

4. (A) contains 0.05 to 250 parts by mass of (B) per 1 part by mass of (A), An oral composition according to any one of claims 1 to 3.

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