JP7523950B2 - Oral Composition - Google Patents

Description

The present disclosure relates to oral compositions and the like, and more particularly to oral compositions and the like containing cetylpyridinium chloride. The contents of all documents described in this specification are incorporated herein by reference.

Cetylpyridinium chloride is a disinfectant that is widely used in oral compositions.

JP 2020-019725 A

Cetylpyridinium chloride (also written as "CPC") is a bactericide that is widely used in oral compositions, but its bactericidal activity can be reduced by saliva.

Therefore, there has been a demand for an oral composition that contains CPC and that inhibits the reduction in the bactericidal activity of CPC caused by saliva when applied to the oral cavity.

After much investigation, the inventors discovered that an oral composition containing a specific nicotinic acid compound together with CPC inhibits the reduction in the bactericidal activity of CPC caused by saliva, and have made further improvements.

The present disclosure includes, for example, the subject matter described in the following sections:
Item 1.
An oral composition comprising cetylpyridinium chloride and at least one nicotinic acid compound selected from the group consisting of nicotinic acid and 2-hydroxynicotinic acid.
Item 2.
Item 2. The oral composition according to item 1, comprising 0.5 to 50 parts by mass of a nicotinic acid compound per part by mass of cetylpyridinium chloride.
Item 3.
Item 3. The oral composition according to item 1 or 2, comprising 0.01 to 0.3% by mass of cetylpyridinium chloride.

A CPC-containing oral composition is provided in which the reduction in the bactericidal activity of CPC caused by saliva is suppressed.

Each embodiment included in the present disclosure will be described in more detail below. The present disclosure preferably includes oral compositions, but is not limited thereto, and includes everything disclosed in this specification that can be recognized by a person skilled in the art.

The oral composition included in the present disclosure contains CPC and a specific nicotinic acid compound. Hereinafter, the oral composition included in the present disclosure may be referred to as the "oral composition of the present disclosure."

The specific nicotinic acid compounds contained in the oral composition of the present disclosure are nicotinic acid and 2-hydroxynicotinic acid. These may be used alone or in combination.

In the oral composition of the present disclosure, the specific nicotinic acid compound is preferably contained in an amount of about 0.5 to 50 parts by mass per part by mass of CPC. The upper or lower limit of the range may be, for example, 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, or 49 parts by mass. For example, the range may be 1 to 40 parts by mass.

In the oral composition of the present disclosure, CPC is preferably contained in an amount of about 0.01 to 0.3% by mass. The upper or lower limit of the 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.

In the oral composition of the present disclosure, the specific nicotinic acid compound is preferably contained in an amount of about 0.01 to 10% by mass. The upper or lower limit of the range is, 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, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.9 5, 1, 1.05, 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, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2 ．8, 2.9, 3, 3.1, 3 ．． 2.3.3 ．4, 6.5, 6.6, 6. It may be 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, 8.9, 9, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, or 9.9% by weight. For example, the range may be 0.02 to 1.9% by weight.

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.

The oral composition of the present disclosure can be manufactured by a known method or a method that can be easily derived from a known method. The oral composition of the present disclosure can also be used, for example, as a medicine, a quasi-drug, or a cosmetic. The form of the oral composition of the present disclosure is not particularly limited, and can be, for example, an ointment, a paste, a gel, a liquid, a spray, a mouthwash, a liquid dentifrice, a toothpaste, a coating agent, or the like (dosage form).

In addition to CPC and the specific nicotinic acid compound, the oral composition of the present disclosure may further contain any optional components that can be incorporated into the oral composition, either alone or in combination of two or more, within a range that does not impair the effects of the present invention.

For example, the surfactant may be a nonionic surfactant, an anionic surfactant, or an amphoteric surfactant.Specific 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 having a polyoxyethylene addition coefficient of 8 to 10 and an alkyl group having 13 to 15 carbon atoms; polyoxyethylene alkylphenyl ethers having a polyoxyethylene addition coefficient of 10 to 18 and an alkyl group having 9 carbon atoms; diethyl sebacate; polyoxyethylene hydrogenated castor oil; fatty acid polyoxyethylene sorbitan; and alkyl glucosides having an alkyl group having 8 to 16 carbon atoms. Examples of anionic surfactants include sulfate ester salts such as sodium lauryl sulfate and sodium polyoxyethylene lauryl ether sulfate; sulfosuccinate salts such as sodium lauryl sulfosuccinate and sodium polyoxyethylene lauryl ether sulfosuccinate; acyl amino acid salts such as sodium cocoyl sarcosine and sodium lauroyl methyl alanine; and sodium cocoyl methyl taurine. Examples of amphoteric surfactants include acetate betaine type surfactants such as lauryl dimethylamino acetate betaine and coconut oil fatty acid amidopropyl dimethylamino acetate betaine; imidazoline type surfactants such as N-cocoyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine sodium; and amino acid type surfactants such as N-lauryl diaminoethyl glycine. Other preferred examples include coconut oil fatty acid monoethanolamide, coconut oil fatty acid diethanolamide, coconut oil fatty acid amido betaine, coconut oil fatty acid amidopropyl betaine, and N-coconut oil fatty acid acyl L-arginine ethyl dl-pyrrolidone carboxylate. These surfactants can be blended alone or in combination of two or more. The amount is usually, for example, 0.1 to 5% by mass of the total composition.

Sweeteners such as saccharin sodium, acesulfame potassium, stevioside, sucralose, neohesperidyl dihydrochalcone, perillartine, thaumatin, aspartyl phenylalanyl methyl ester, and p-methoxycinnamic aldehyde may also be added. These may be used alone or in combination of two or more. These may be added in an amount of, for example, 0.01 to 1% by mass based on the total amount of the composition.

As the binder, for example, one or more of the following may be used in combination: cellulose derivatives such as sodium carboxymethylcellulose, carboxymethylethylcellulose salts, hydroxyethylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose; microbial polymers such as xanthan gum and gellan gum; natural polymers or natural rubbers such as tragacanth gum, karaya gum, gum arabic, carrageenan, and dextrin; synthetic polymers such as polyvinyl alcohol and polyvinylpyrrolidone; inorganic binders such as thickening silica and veegum; and cationic binders such as O-[2-hydroxy-3-(trimethylammonio)propyl]hydroxyethylcellulose chloride.

In addition, sorbitol, glycerin, propylene glycol, xylitol, maltitol, lactitol, polyoxyethylene glycol, etc. can be used alone or in combination of two or more types as humectants.

Preservatives that can be used include parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, sodium benzoate, phenoxyethanol, and alkyldiaminoethylglycine hydrochloride, either alone or in combination of two or more.

Coloring agents may include legal pigments such as Blue No. 1, Yellow No. 4, Red No. 202, and Green No. 3, mineral pigments such as ultramarine, enhanced ultramarine, and Prussian blue, and titanium oxide, either alone or in combination of two or more kinds.

As a pH adjuster, citric acid, phosphoric acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or chemically possible salts thereof, sodium hydroxide, etc. may be blended. These may be blended alone or in combination of two or more kinds 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 blended is, for example, 0.01 to 2% by weight.

As a medicinal ingredient, a bactericide other than cetylpyridinium chloride may be blended. Examples include cationic bactericides such as benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, and chlorhexidine gluconate, amphoteric bactericides such as dodecyldiaminoethylglycine, nonionic bactericides such as triclosan and isopropylmethylphenol, and hinokitiol. Furthermore, medicinal ingredients other than bactericides may be blended. For example, aluminum lactate, potassium nitrate, vitamin E such as dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate, sodium fluoride, etc. may be blended. The medicinal ingredients may be blended alone or in combination of two or more.

As bases, for example, alcohols, silicone, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, plastibase, etc. can be added alone or in combination of two or more.

Note that the above optional ingredients are merely examples and do not limit the optional ingredients that may be used.

Since the oral composition of the present disclosure contains the specific nicotinic acid compound, the decrease in the bactericidal activity of CPC due to saliva is suppressed. Therefore, the time required for sterilization is shorter than when the specific nicotinic acid compound is not contained. Therefore, it is possible to shorten the time required for oral care. In addition, the bactericidal activity of CPC is preferably used in oral compositions to sterilize periodontal disease bacteria, for example. Therefore, although not particularly limited, the oral composition of the present disclosure can be preferably used for subjects carrying oral periodontal disease bacteria (particularly periodontal disease patients). Furthermore, since the decrease in the bactericidal activity of CPC due to saliva varies from person to person (for example, some people experience a significant decrease in the bactericidal activity of CPC due to saliva, while others experience a mild decrease in the bactericidal activity of CPC due to saliva), although not particularly limited, the oral composition of the present disclosure can be preferably used for subjects for which the decrease in the bactericidal activity of CPC due to saliva is required (more specifically, for example, subjects for whom the bactericidal activity of CPC is decreased by saliva, subjects suffering from oral diseases caused by bacteria such as periodontal disease, etc.). Furthermore, subjects include not only humans but also non-human mammals. For example, pets and livestock may be included. More specifically, for example, dogs, cats, monkeys, cows, horses, pigs, sheep, goats, mice, rats, etc. may be included.

The present disclosure also includes a method for inhibiting the reduction in the bactericidal activity of CPC caused by saliva, which includes using a combination of CPC and the specific nicotinic acid compound, and a method for producing a composition for the oral cavity, which includes incorporating CPC and the specific nicotinic acid compound into a composition.

In this specification, the term "comprising" includes "consisting essentially of" and "consisting of." In addition, the present disclosure includes any combination of the constituent elements described in this specification.

Furthermore, the various characteristics (properties, structures, functions, etc.) described for each embodiment of the present disclosure above may be combined in any way to identify the subject matter encompassed by the present disclosure. In other words, the present disclosure encompasses all subject matter consisting of any combination of the combinable characteristics described in this specification.

The following provides a more detailed explanation of the embodiments of the present disclosure, but the embodiments of the present disclosure are not limited to the following examples.

Saliva collection: Each subject (subjects A to D) was asked to brush their teeth with a dentifrice that did not contain surfactants or bactericides, and 10 mL of saliva (non-irritating saliva) was collected from each subject. The collected saliva was stored in a refrigerator, and immediately before use, it was sucked up and discharged five times using a 23G injection needle and a 10 mL syringe (both manufactured by Terumo Corporation).

Preparation of test drug solutions Test drug solutions were prepared containing 0.05% (w/v) cetylpyridinium chloride and 0.1, 0.25, or 0.5% (w/v) of each nicotinic acid compound. In preparing the test drug solutions, aqueous solutions were prepared and used for solutions containing nicotinic acid, isonicotinic acid, methyl nicotinate, and nicotinamide. For solutions containing 2-hydroxynicotinic acid and 2-chloronicotinic acid, a DMSO solution with a final concentration of 5% (v/v) was prepared and diluted 10-fold with water.

In addition, the concentration of each test drug solution is shown in % (w/v), but since this is almost the same as the value of % (w/w) (% (w/w) is only slightly larger), it can be interpreted as % (w/w) (i.e., mass %). More specifically, for example, the density of a 5% (v/v) DMSO solution calculated from JIS K 9702 and JIS Z 8804 is 0.994 g/cm ³ , the above cetylpyridinium chloride 0.05% (w/v) can be calculated as 0.05030181% (w/w), the above nicotinic acid compounds 0.25% (w/v) can be calculated as 0.25150905 mass%, and 0.5% (w/v) can be calculated as 0.50301810 mass%.

Bactericidal test: 200 μL of the test drug solution was dispensed into row A of a 96-well plate, and 200 μL of TSB medium for CPC inactivation and oral bacterial culture was dispensed into rows BH.

Since TSB medium can inactivate CPC, the sterilization time can be adjusted by adjusting the timing of adding the medium. The TSB medium was prepared by dissolving 30 g of Tripticase Soy Broth (TSB), 1 g of Yeast Extract, 1 g of Hemin/menadion solution, 0.7 g of lecithin, and 5 g of Tween 80 in distilled water, measuring up to 1 L, and sterilizing the solution in an autoclave. The Hemin/menadion solution was prepared by dissolving 0.25 g of Hemin in 5 ml of 1N NaOH, adding 20 ml of distilled water, and then mixing the solution with 0.025 g of menadion (Vitamin K3) dissolved in 25 ml of 99% ethanol.

20 μL of saliva was added to row A, pipetted, and then 20 μL was added from row A to rows B to H at each time point. More specifically, the measurement started when 20 μL of saliva was added to row A and mixed by pipetting. 20 μL of the solution from row A was added to row B after 30 seconds, row C after 60 seconds, row D after 90 seconds, row E after 120 seconds, row F after 180 seconds, row G after 240 seconds, and row 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 medium was visually turbid, it was determined that bacteria had grown and the bacteria in the solution had not been completely killed.

After 30 seconds, 60 seconds, 90 seconds, 120 seconds, 180 seconds, 240 seconds, and 300 seconds, each solution collected from row A was judged, and the time when the medium did not become turbid and the bacteria in the solution were killed was defined as the sterilization time.

Table 1 shows the relative bactericidal time when each nicotinic acid compound was added, assuming that the bactericidal time for each subject's saliva with cetylpyridinium chloride 0.05% (w/v) alone is 100%. For example, if the bactericidal time when cetylpyridinium chloride 0.05% (w/v) is mixed with subject A's saliva is 120 seconds, and the bactericidal time when the test drug solution containing cetylpyridinium chloride 0.05% (w/v) and nicotinic acid 0.5% (w/v) is mixed with subject A's saliva is 60 seconds, the relative bactericidal time in this case is 50%. Note that blank spaces for the relative bactericidal time value indicate that it was not considered.

A sample formulation is shown below. Note that the values for each component in the table showing the sample formulation are in mass percent.

Claims (3)

Contains cetylpyridinium chloride and at least one nicotinic acid compound selected from the group consisting of nicotinic acid and 2-hydroxynicotinic acid;
Contains 0.01 to 0.3% by mass of cetylpyridinium chloride,
The composition contains 1 to 20 parts by mass of a nicotinic acid compound per 1 part by mass of cetylpyridinium chloride.
Oral compositions. The oral composition according to claim 1, which contains 0.02 to 0.15% by mass of cetylpyridinium chloride. The oral composition according to claim 1 or 2 , which contains 0.05 to 1 % by mass of a nicotinic acid compound.