JP7333446B2 - oral composition - Google Patents

Description

The present invention relates to oral compositions.

BACKGROUND ART Conventionally, various medicinal ingredients have been used in oral compositions in order to impart pharmacological actions that contribute to prevention, prevention, and improvement of various oral diseases such as dental caries and periodontal disease. Among them, in order to increase the amount of medicinal ingredients adsorbed to the gums and oral mucosa, it is effective to adopt a technique to form a lamellar structure in the composition by using a specific higher alcohol and a nonionic surfactant together. Some are known and oral compositions have been developed that employ such techniques.

For example, Patent Document 1 discloses an oral composition comprising a combination of a specific higher alcohol, a nonionic surfactant, and a medicinal ingredient while using a zinc compound effective in suppressing bad breath and preventing gingivitis. In addition to suppressing the metallic taste of zinc compounds, it is intended to increase the amount of medicinal ingredients adsorbed to the gums and oral mucosa. In addition, Patent Document 2 also discloses an oral composition in which a specific amount of an oil-soluble medicinal ingredient and a surfactant containing a specific higher alcohol and a specific nonionic surfactant are used in combination. While ensuring high adsorption of oil-soluble medicinal ingredients to the inner mucosa, the storage stability of viscosity is enhanced.

JP 2018-197198 A JP 2017-214347 A

On the other hand, in the composition described in the above patent document, as the content of the higher alcohol increases, the flavor becomes poorer when applied to the oral cavity, and in addition, the composition becomes oily in use. In order to avoid this, it is preferable to reduce the content of the higher alcohol as much as possible.
However, the present inventors have found that if an attempt is made to increase the content of glycyrrhetinic acid while reducing the content of higher alcohol, glycyrrhetinic acid precipitates during storage of the composition.

That is, the present invention relates to an oral composition that can effectively suppress the precipitation of glycyrrhetinic acid even when the content of higher alcohol is restricted.

Therefore, as a result of various studies, the present inventors have found that a cellulose derivative containing a nonionic surfactant and water along with glycyrrhetinic acid and having a specific SP value while limiting the content of higher alcohols within an extremely limited range. and a higher alcohol in a specific quantitative relationship to obtain an oral composition that can effectively suppress the precipitation of glycyrrhetinic acid.

Accordingly, the present invention provides the following components (A), (B), (C), (D) and (E):
(A) Glycyrrhetinic acid 0.18% by mass to 0.5% by mass (B) Higher alcohol having 12 to 22 carbon atoms 1.5% by mass to 8.5% by mass (C) Nonionic surfactant (D ) water (E) contains a cellulose derivative with an SP value of 9.3 or more and 12.0 or less, and the mass ratio of the content of component (B) to the content of component (E) ((B)/( E)) is 0.6 or more and 70 or less to provide an oral composition.

According to the composition for oral cavity of the present invention, even if the content of higher alcohol is restricted within an extremely limited range, it is effective to prevent unnecessary precipitation of glycyrrhetinic acid during storage of the composition. can be suppressed to Therefore, it is possible to fully enjoy the efficacy of glycyrrhetinic acid without reducing the amount of adsorption to the gums and oral mucosa, and it is also possible to ensure a good feeling in use and applicability of the composition.

1 is a photograph of the composition obtained in Example 1. FIG. 1 is a photograph of a composition obtained in Comparative Example 1. FIG.

The present invention will be described in detail below.
In the present specification, the term "good feeling in use" means that when the oral composition of the present invention is applied in the oral cavity, it has a moderate flavor, no oily feeling in use, and a smooth feeling in the oral cavity. It means that the feeling of melting and spreading is brought.

The oral cavity composition of the present invention contains 0.18% by mass or more and 0.5% by mass or less of glycyrrhetinic acid as the component (A). Glycyrrhetinic acid of component (A) has anti-inflammatory action, alveolar bone resorption inhibitory action, histamine release inhibitory action and the like. Such component (A) can be effectively adsorbed to the gums and oral mucosa to provide preventive and ameliorative action against periodontitis, periodontal disease, and the like.

The content of component (A) in the oral composition of the present invention is from the viewpoint of ensuring the efficacy of component (A) effectively and efficiently, and the content of component (B) described later is limited. However, since the precipitation of component (A) can be effectively suppressed, the content of component (A) can be increased. , preferably 0.22% by mass or more, more preferably 0.25% by mass or more. In addition, the content of component (A) is 0.5% by mass or less in the oral cavity composition of the present invention from the viewpoint of effectively ensuring the effect of suppressing precipitation of component (A), preferably It is 0.4% by mass or less, more preferably 0.35% by mass or less. The content of component (A) in the oral composition of the present invention is 0.18% by mass or more and 0.5% by mass or less, preferably 0.22 to 0.4% by mass. , more preferably 0.25 to 0.35% by mass. In addition, the content of glycyrrhetinic acid in the present invention refers to the acid conversion when the glycyrrhetinic acid is in the form of a salt.

The oral cavity composition of the present invention contains 1.5 to 8.5% by mass of a higher alcohol having 12 to 22 carbon atoms as the component (B). By containing the component (B) in such a limited amount, it is possible to secure a good feeling of use of the composition and at the same time secure a high adsorption amount of the component (A) to the gums and oral mucosa. can be done.

The higher alcohol having 12 to 22 carbon atoms of component (B) includes one or more selected from cetanol, stearyl alcohol, lauryl alcohol, myristyl alcohol and behenyl alcohol. Among them, higher alcohols having 14 to 20 carbon atoms are preferable, and one or two selected from cetanol (b1) and stearyl alcohol (b2) are more preferable from the viewpoint of ensuring a good feeling of use of the composition. .

From the viewpoint of effectively suppressing the precipitation of component (A), the content of component (B) is 1.5% by mass or more, preferably 2.5% by mass, in the oral composition of the present invention. or more, more preferably 3% by mass or more, still more preferably 4% by mass or more, and even more preferably 6% by mass or more. In addition, the content of component (B) in the composition for oral cavity of the present invention is 8, from the viewpoint of ensuring a good feeling of use of the composition, eliminating oily feeling of use and improving flavor development. 0.5% by mass or less, preferably 8.4% by mass or less, and more preferably 8.3% by mass or less. The content of component (B) in the oral composition of the present invention is 1.5% by mass or more and 8.5% by mass or less, preferably 2.5 to 8.5% by mass. , more preferably 3 to 8.4% by mass, still more preferably 4 to 8.3% by mass, still more preferably 6 to 8.3% by mass.

Here, when the oral composition of the present invention contains cetanol (b1) and stearyl alcohol (b2) as component (B), the mass of the content of component (b1) and the content of component (b2) From the viewpoint of effectively suppressing precipitation of component (A), the ratio ((b1)/(b2)) is preferably 0.5 or more, more preferably 0.7 or more, and still more preferably 1 or more. , preferably 10 or less, more preferably 8 or less, and even more preferably 6 or less.
In addition, component (B) other than component (b1) and component (b2) can be contained, and examples of such components include lauryl alcohol, myristyl alcohol, and behenyl alcohol.

The oral composition of the present invention contains a nonionic surfactant as component (C). As a result, even when the content of component (B) is limited, a high adsorption amount of component (A) to the gums and oral mucosa can be ensured.

Examples of such component (C) include sorbitan monocaprate, sorbitan monoundecylate, sorbitan monolaurate, sorbitan monotridecylate, sorbitan monomyristate, sorbitan monopalmitate, sorbitan monooleate, sorbitan trioleate, sorbitan tetraoleate, Sorbitan fatty acid esters such as sorbitan sesquioleate, sorbitan monostearate, and sorbitan tristearate; polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monomyristate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene monostearate One or more selected from polyoxyethylene sorbitan fatty acid esters such as sorbitan and polyoxyethylene sorbitan monooleate can be used.

Component (C) contains one or more selected from polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate and polyoxyethylene sorbitan monooleate from the viewpoint of enhancing low-temperature stability. is preferred.

As component (C), sorbitan monooleate, sorbitan sesquioleate, sorbitan monostearate, polyoxyethylene sorbitan monopalmitate, and monostearin are selected from the viewpoint of the absorbability of component (A) to the gums and oral mucosa. One or more selected from polyoxyethylene sorbitan acid and polyoxyethylene sorbitan monooleate are preferred.
In particular, the combined use of polyoxyethylene sorbitan fatty acid ester and sorbitan fatty acid ester, particularly the combined use of polyoxyethylene sorbitan monostearate and sorbitan monostearate, effectively suppresses precipitation of component (A). can do.

The content of component (C) is in the oral composition of the present invention from the viewpoint of effectively ensuring the effect of suppressing the precipitation of component (A) and effectively increasing the adsorption performance to the gums and oral mucosa. Furthermore, it is preferably 0.2% by mass or more, more preferably 0.4% by mass or more, still more preferably 0.5% by mass or more, and even more preferably 1.2% by mass or more. In addition, the content of component (C) is preferably 10% by mass or less in the oral composition of the present invention from the viewpoint of ensuring the stability of the composition and maintaining the balance with flavor. , more preferably 8% by mass or less, still more preferably 6% by mass or less, and even more preferably 3% by mass or less. The content of component (C) in the oral composition of the present invention is preferably 0.2 to 10% by mass, more preferably 0.4 to 8% by mass, and still more preferably 0 0.5 to 6% by mass, more preferably 1.2 to 3% by mass.

In the oral cavity composition of the present invention, the content of component (B) and the mass ratio of component (C) ((B)/(C)) is determined from the viewpoint of effectively suppressing precipitation of component (A). , preferably 1 to 10, more preferably 2 to 9, still more preferably 3 to 8, still more preferably 4 to 6.

The oral composition of the present invention contains water as component (D). The water of component (D) in the present invention is not only purified water directly blended in the oral composition, but also included in each blended component such as 70% sorbitol solution (aqueous solution) used when formulating. means the total water contained in the oral composition, including the water contained in the oral composition. By containing water as component (D), each component can be well dispersed or dissolved while ensuring good shape retention as an oral composition, and precipitation of component (A) can be suppressed. can contribute.

The content of component (D) in the oral composition of the present invention is preferably 30% by mass or more, more preferably 40% by mass or more, still more preferably 50% by mass or more, and more preferably is 55% by mass or more, preferably 95% by mass or less, more preferably 92% by mass or less, still more preferably 80% by mass or less, and more preferably 70% by mass or less. The content of component (D) in the oral composition of the present invention is preferably 30 to 95% by mass, more preferably 40 to 92% by mass, and still more preferably 50 to 80% by mass. and more preferably 55 to 70% by mass.

The content of the component (D) in the oral cavity composition of the present invention, that is, the water content, can be calculated from the water content and the water content in the ingredients. can be measured in As the Karl Fischer moisture meter, for example, a trace moisture measuring device (manufactured by Hiranuma Sangyo Co., Ltd.) can be used. With this device, 5 g of the oral composition is taken, suspended in 25 g of anhydrous methanol, and 0.02 g of this suspension is aliquoted to measure the water content.

The oral composition of the present invention contains a cellulose derivative having an SP value of 9.3 or more and 12.0 or less as the component (E). The cellulose derivative of component (E) is one type of so-called viscosity modifier, and after adopting a viscosity modifier close to the SP value of component (A), component (E) is added to component (B). By containing it in an appropriate mass ratio with respect to the amount, while the content of component (B) is limited within an extremely limited range, component (A) will not precipitate during storage of the composition. can be effectively suppressed.

The SP value of component (E) effectively suppresses precipitation of component (A) during storage of the composition even if the content of component (B) is limited within an extremely limited range. In addition to the viewpoint, in order to ensure the suppression effect more sufficiently, it is also a matter found by the present inventors, and from the viewpoint that it is desirable that the SP value is close to the SP value of the component (A), 9.3 or more , preferably 9.5 or more, more preferably 9.8 or more, 12.0 or less, preferably 11.5 or less, more preferably 11 or less, and still more preferably is 10 or less.

The SP value of ^the component ( ^E ) is the value of the so-called solubility parameter δ. is a given material constant. From this value, the relative polarity of the substance can be estimated, and the SP value is a value determined by actual measurement or calculation by various methods. In the present invention, the SP value of the component (E) is determined by the "Okitsu formula (Journal of the Adhesion Society of Japan, vol.29, No.5, 204-211 (1993))", and the component (E) are two or more cellulose derivatives, the SP value of each cellulose derivative alone must be within the above range.

A hydroxycellulose derivative is preferable as such component (E). The hydroxycellulose derivative means cellulose ethers obtained by etherification of at least a part of hydroxyl groups of cellulose with hydroxyalkyl groups. Specifically, one or more selected from hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropylmethyl cellulose can be used. Among them, hydroxyethyl cellulose, and hydroxypropylmethylcellulose are preferred. This can effectively promote the formation of an α-gel having a lamellar structure.

From the viewpoint of effectively suppressing the precipitation of component (A) while the content of component (B) is limited within a very limited range, the content of component (E) is the oral composition of the present invention. Among them, it is preferably 0.3% by mass or more, more preferably 0.6% by mass or more, and still more preferably 1.2% by mass or more. In addition, from the viewpoint of effectively suppressing the precipitation of component (A), the content of component (E) in the oral cavity composition of the present invention is preferably 2.5% by mass or less, more preferably 2% by mass. % by mass or less, more preferably 1.6% by mass or less. The content of component (E) in the oral composition of the present invention is preferably 0.3% by mass or more and 2.5% by mass or less, more preferably 0.6 to 2% by mass. , more preferably 1.2 to 1.6% by mass.

In the oral composition of the present invention, the mass ratio of the content of component (B) to the content of component (E) ((B)/(E)) is such that the content of component (B) is extremely limited. Within the range, from the viewpoint of effectively suppressing precipitation of component (A), it is 0.6 or more, preferably 1 or more, more preferably 2 or more, and still more preferably 3 That's it. In addition, the mass ratio ((B)/(E)) of the content of component (B) to the content of component (E) is 70 or less from the viewpoint of effectively suppressing precipitation of component (A). is preferably 30 or less, more preferably 20 or less. The mass ratio ((B)/(E)) of the content of component (B) to the content of component (E) is 0.6 or more and 70 or less, preferably 0.6 or more and 30 or less. , more preferably 1 to 10, still more preferably 2 to 9, and even more preferably 3 to 8.5.

In the oral composition of the present invention, the mass ratio of the content of component (E) to the content of component (A) ((E)/(A)) is such that the content of component (B) is extremely limited. Within the range, from the viewpoint of effectively suppressing precipitation of component (A), it is preferably 0.5 or more, more preferably 1.2 or more, and still more preferably 1.5 or more. be. In addition, the mass ratio of the content of component (E) to the content of component (A) ((E)/(A)) is preferably 20 or less from the viewpoint of effectively suppressing precipitation of component (A). , more preferably 15 or less, and still more preferably 10 or less. The mass ratio ((E)/(A)) between the content of component (E) and the content of component (A) is preferably 0.5 or more and 20 or less, more preferably 1.2 to 15, more preferably 1.5-10.

In addition, in the oral composition of the present invention, while the content of the component (B) is limited within an extremely limited range, the precipitation of the component (A) is effectively suppressed, and the gums and oral mucosa are From the viewpoint of effectively increasing the adsorption amount, it is preferable to limit the content of viscosity modifiers other than component (E).
Viscosity modifiers other than component (E) include cellulose-based viscosity modifiers other than cellulose derivatives having a specific SP value, and viscosity modifiers other than cellulose-based binders. It is meant to include agents referred to as "agents". Specifically, for example, sodium carboxymethylcellulose, carboxyvinyl polymer, ethyl cellulose, sodium alginate, carrageenan, xanthan gum, sodium polyacrylate, pectin, agar, tragacanth gum, gum arabic, guar gum, karaya gum, locust bean gum, gela gum, tamarid gum, psyllium seed gum and the like.

The content of viscosity modifiers other than component (E) is preferably less than 0.2% by mass, more preferably less than 0.1% by mass, and still more preferably less than 0.1% by mass in the oral composition of the present invention. is less than 0.05% by mass, or the oral composition of the present invention preferably contains substantially no viscosity modifiers other than component (E).

In the composition for oral cavity of the present invention, it is preferable to limit the content of the oily component from the viewpoint of effectively suppressing precipitation of the component (A).
The oil-based component means an oil-soluble component other than the components (A), (B), and (C), and an oil-soluble component other than surfactants and perfumes. , liquid paraffin, petroleum jelly, mineral oil, light liquid paraffin, paraffin wax, ceresin, microcrystalline wax, carnauba wax, beeswax, squalane, hydrocarbon oils such as squalene; isopropyl myristate, isopropyl palmitate, propyl adipate, sebacic acid Ester oils such as diethyl and glycerin fatty acid esters; Triglycerides and vegetable oils such as olive oil, rapeseed oil, shea butter and rice bran oil containing triglycerides; Silicone oils; Preservatives such as methyl parahydroxybenzoate and ethyl parahydroxybenzoate; etc.

The content of these oily components in the oral composition of the present invention is preferably less than 0.15% by mass, more preferably less than 0.1% by mass, and even more preferably less than 0.05% by mass. Alternatively, the oral composition of the present invention preferably does not substantially contain an oily component.

In addition, from the viewpoint of effectively suppressing the precipitation of component (A), the oral composition of the present invention contains polyvalent metals selected from strontium, magnesium, aluminum, calcium, zirconium, iron, copper, zinc, and manganese. It is preferable to limit the content. The content of such a polyvalent metal, in terms of metal atoms, is preferably 2% by mass or less, more preferably 1% by mass or less, and still more preferably 0.5% by mass in the oral composition of the present invention. % by weight or less, more preferably 0.1% by weight or less, or the oral composition of the present invention is selected from strontium, magnesium, aluminum, calcium, zirconium, iron, copper, zinc, and manganese. It is preferably substantially free of polyvalent metals.

The composition for oral cavity of the present invention contains sugar alcohols such as sorbitol, xylitol, erythritol, reduced palatinose, and mannitol as components other than the above components, as long as the effects of the present invention are not impaired; humectants such as glycerin; ; medicinal ingredients other than component (A) such as tocopherol acetate; surfactants other than component (C); antibacterial agents such as cetylpyridinium chloride; pH adjusters such as sodium hydroxide; can contain.

The pH of the oral cavity composition of the present invention at 25°C is preferably 8 or higher, more preferably 8.3 or higher, and still more preferably 8.0 or higher, from the viewpoint of effectively suppressing precipitation of component (A). It is 5 or more, preferably 10 or less, more preferably 9.8 or less, and still more preferably 9.6 or less. The pH of the oral composition of the present invention at 25° C. is preferably 8 or more and 10 or less, more preferably 8.3 to 9.8, still more preferably 8.5 to 9.6. .

Preferred forms of the oral composition of the present invention include coating agents, toothpastes, gargles, liquid dentifrices and the like. Among them, coating agents and toothpastes are preferable from the viewpoint of effectively suppressing precipitation of component (A) and sufficiently spreading the oral composition of the present invention to the gums or the intraoral mucosa.
The method of application to the oral cavity may be any of application, brushing with a toothbrush, or gargling, and application using fingers or tools to the gums or brushing with a toothbrush is preferred.

The method for producing the oral cavity composition of the present invention is not particularly limited, and the above ingredients may be appropriately mixed by a conventional method.

EXAMPLES The present invention will be specifically described below based on examples. In addition, unless otherwise indicated in the table, the content of each component indicates % by mass.

[Examples 1 to 8, Comparative Examples 1 to 4]
Each oral composition was produced according to the formulations shown in Tables 1 and 2.
Using the obtained composition for oral cavity, measurement and evaluation were performed according to the following methods.
Results are shown in Tables 1 and 2.

<<Measurement of pH>>
90 mL of freshly boiled and cooled water was added to 10 g of each oral composition, and the mixture was shaken well (25° C.), and pH was measured using a pH/ION METER F53 (manufactured by HORIBA).

《Evaluation of stability》
Each oral composition was filled in an aluminum laminate tube and stored in a thermostat at 50° C. for 1 month. In addition to visually confirming the precipitation of component (A), the composition was squeezed onto a slide glass and sandwiched between slides, and the presence or absence of precipitates of component (A) was confirmed by microscopic observation (100 times). Evaluation was made according to the following criteria.
The obtained evaluation results are summarized in the table as "appearance of composition/precipitation of component (A)".
Appearance evaluation of composition A: Composition is uniform and no separation is observed B: Composition is separated and separation is observed Evaluation of precipitation of component (A) A: Both by visual observation and microscopic observation , Presence of precipitate was not confirmed B: Presence of precipitate was confirmed by microscopic observation C: Presence of precipitate was confirmed by visual inspection

<<Evaluation of feeling in use and applicability>>
0.3 g of each of the oral compositions shown in Table 2 was applied to a finger and evaluated for feel in use and applicability when applied to the gums.
Since it was confirmed that all of the compositions for oral cavity of the examples shown in Table 2 had a good feeling in use, Table 2 shows only the evaluation of applicability.

Claims (10)

The following components (A), (B), (C), (D), and (E):
(A) Glycyrrhetinic acid 0.18% by mass or more and 0.5% by mass or less (B) Higher alcohol having 12 to 22 carbon atoms, including cetanol (b1) and stearyl alcohol (b2) 1.5% by mass or more 8. 5% by mass or less (C) Nonionic surfactant (D) Water (E) A cellulose derivative having an SP value of 9.3 or more and 12.0 or less 0.6% or more and 2.5% or less by mass. Paraffin content is less than 0.15% by mass,
The mass ratio of the content of component (B) to the content of component (E) ((B)/(E)) is 0.6 or more and 70 or less, and the content of component (B) and component (C) is 3.8 to 10, and the mass ratio of the content of component (b1) to the content of component (b2) ((b1)/(b2) ) is 0.5 or more and 10 or less. The oral composition according to Claim 1, wherein component (C) is one or more selected from sorbitan fatty acid esters and polyoxyethylene sorbitan fatty acid esters. The composition for oral cavity according to claim 1 or 2, wherein the content of component (C) is 0.2% by mass or more and 10% by mass or less. The oral composition according to any one of claims 1 to 3 , wherein the content of component (D) is 30% by mass or more and 95% by mass or less. 5. The mass ratio ( ( E) / (A) ) of the content of component (E ) to the content of component (A) is 0.5 or more and 20 or less, according to any one of claims 1 to 4 . oral composition. The content of oily components other than surfactants and fragrances is less than 0.15% by mass, or does not contain oily components other than surfactants and fragrances, according to any one of claims 1 to 5 . Oral composition. The content of the viscosity modifier other than the component (E) is 2% by mass or less, or the oral cavity according to any one of claims 1 to 6 , which does not contain a viscosity modifier other than the component (E). Composition. The content of polyvalent metals selected from strontium, magnesium, aluminum, calcium, zirconium, iron, copper, zinc, and manganese is 0.1 % by mass or less , or does not contain any of claims 1 to 7 . 1. The oral composition according to item 1. The oral composition according to any one of claims 1 to 8 , which has a pH of 8 or more and 10 or less at 25°C. The content of oil-soluble components other than components (A), (B), (C), surfactants, fragrances, and liquid paraffin is less than 0.15% by mass, or oil-soluble components The oral composition according to any one of claims 1 to 9, which does not contain