WO2021132067A1

WO2021132067A1 - Composition for oral cavity

Info

Publication number: WO2021132067A1
Application number: PCT/JP2020/047387
Authority: WO
Inventors: 慶貴大野; 勇介川延; 彩佳岩崎
Original assignee: ライオン株式会社
Priority date: 2019-12-24
Filing date: 2020-12-18
Publication date: 2021-07-01
Also published as: CN114867455B; CN114867455A; JP2021098678A; JP7342688B2

Abstract

Provided is a good-tasting composition for the oral cavity that contains allantoin and/or tranexamic acid. The composition, even when subjected to long-term storage at high temperatures, is resistant to coloration or discoloration of the formulation and exhibits an excellent stability in the appearance of the formulation and is resistant to an unpleasant taste.　The composition for the oral cavity contains (A) at least one selected from allantoin and tranexamic acid, (B) at least one selected from aldehyde group-bearing compounds and menthofuran, and (C) a polyacrylate salt having a weight-average molecular weight of 1,000-20,000, wherein (C)/(A) as the mass ratio is 0.1-21.

Description

Oral composition

The present invention relates to an oral composition containing allantoin and / or tranexamic acid, which suppresses coloring and discoloration even after storage, has excellent appearance stability, and has a good taste.

Inflammation relief is effective for the prevention of periodontal disease, and it is known that an active ingredient having an amino group such as tranexamic acid or allantoin is added to an oral composition as an anti-inflammatory agent, for example.
On the other hand, in the oral composition, a fragrance is indispensable for preparing a highly palatable preparation, and among them, a compound having an aldehyde group and mentoflan are important components, and the highly palatable oral composition. It is an indispensable fragrance ingredient for the preparation of.
However, when a fragrance is blended with an active ingredient having an amino group in the oral composition, it may be difficult to maintain the appearance of the preparation depending on the fragrance component species, and when a compound having an aldehyde group is blended, the composition has an amino group. The reaction between the active ingredient and the compound having an aldehyde group causes a problem of coloring and discoloring the oral composition, and ensuring the appearance stability has become an issue.

In Patent Document 1 (Patent No. 5842565), by adding sodium lauryl sulfate to a mouthwash composition containing tranexamic acid, which is an active ingredient having an amino group, and synamic aldehyde, 3 at room temperature. It suppresses discoloration after storage for months. Further, in Patent Document 2 (Japanese Patent Publication No. 62-16926), by adding a specific compatible aldehyde-based fragrance as an aldehyde-based fragrance to a toothpaste containing tranexamic acid, coloring after storage at 50 ° C. for 2 days is performed. , Suppresses discoloration.
However, in the conventional technique, it is not possible to suppress the coloring and discoloration of the oral composition due to the reaction between the active ingredient having an amino group and the fragrance component such as a compound having an aldehyde group even if it is stored at a high temperature for a long period of time. It is difficult, and a technique for further suppressing coloring and discoloration over time has been desired.

Japanese Patent No. 5842565 Special Publication No. 62-16926 Japanese Unexamined Patent Publication No. 2019-99483

The present invention has been made in view of the above circumstances, and is an oral composition containing allantoin and / or tranexamic acid, which suppresses coloring and discoloration of the pharmaceutical product even when stored at a high temperature for a long period of time, has excellent appearance stability, and has a good taste. The purpose is to provide goods.

As a result of diligent studies to achieve the above object, the present inventors have made an oral composition containing allantin or tranexamic acid having an amino group and a compound or mentoflan having an aldehyde group as a fragrance component. When a low molecular weight polyacrylate is blended in a specific ratio, it has an excellent effect of suppressing coloration and discoloration over time, which suppresses discoloration (coloring and discoloration) of the preparation even when stored at high temperature for a long period of time and stabilizes the appearance. It has been found that the sex is improved, the dislike is suppressed, the good taste is maintained, high palatability is ensured, and excellent appearance stability can be provided.
That is, according to the present invention, (A) one or more selected from allantoin and tranexamic acid, (B) one or more selected from compounds having an aldehyde group and mentoflan, and (C) weight average molecular weight 1, An oral composition containing 000 to 20,000 polyacrylates and having a mass ratio of (C) / (A) of 0.1 to 21 is colored even after long-term storage at high temperature. It has been found that discoloration is suppressed, the appearance is stable, and the taste is good, and the present invention has been made.

Not only when a compound having an aldehyde group as a fragrance component is added to an oral composition containing allantoin or tranexamic acid as an anti-inflammatory agent, but also when mentoflan is added, the formulation is colored and discolored over time, and the appearance is changed. There was a problem of reduced stability. However, in the present invention, in an oral composition, particularly a dentifrice composition, by combining the components (A) and (B) and the component (C), it is generated by the reaction of the component (A) and the component (B). Coloring and discoloration of the pharmaceutical product over time were suppressed by the component (C), and the appearance stability was excellent. In this case, the component (C) has a mass ratio of (C) / (A) within a specific range, and surprisingly, specifically as a discoloration inhibitor for the combined system of the components (A) and (B). It acts, thereby ensuring a good taste without expressing the peculiar dislike of the component (C) itself, suppressing discoloration (coloring, discoloration) of the formulation even after long-term storage at high temperature, and in the examples described later. As shown, the suppression of discoloration of the pharmaceutical product was suppressed even after storage at 60 ° C. for 1 month, and an excellent effect of suppressing discoloration could be provided.
As the binder for the oral composition, polyacrylic acid or a salt thereof having a weight average molecular weight of 100,000 or more and usually about 300,000 is generally used. On the other hand, in the present invention, the above-mentioned exceptionally remarkable action and effect could be imparted by (C) a specific polyacrylate having a low molecular weight.
The effect of the present invention is that the mass ratio of (C) / (A) can be obtained within a specific range by combining the components (A), (B) and (C). As shown, if the component (C) is not blended, the discoloration suppressing effect is poor even if the sodium polyacrylate having a weight average molecular weight of 300,000 is blended (Comparative Examples 1 and 2), and the component (C) is blended. However, if the mass ratio of (C) / (A) was inappropriate, the discoloration suppressing effect or the taste (no dislike) was poor (Comparative Examples 3 and 4).
In addition, Patent Document 3 (Japanese Unexamined Patent Publication No. 2019-99483) describes that by combining a specific low molecular weight polyacrylate with menthol and a specific aldehyde-based fragrance, the irritation sensation is suppressed and a refreshing feeling of use is imparted. is there. On the other hand, the present invention is the suppression of discoloration and the suppression of sarcasm of the combined system of the components (A) and (B) by the component (C).

Therefore, the present invention provides the following oral compositions.
[1]
(A) One or more selected from allantoin and tranexamic acid,
It contains (B) one or more selected from compounds having an aldehyde group and mentoflan, and (C) polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less, and (C) / (A) is the mass. Oral compositions having a ratio of 0.1 to 21.
[2]
The oral composition according to [1], wherein the component (B) is selected from trans-2-hexenal, phenylacetaldehyde, citral and mentoflan.
[3]
In [1] or [2], the component (A) is contained in an amount of 0.005 to 1% by mass, the component (B) is contained in an amount of 0.0001 to 0.5% by mass, and the component (C) is contained in an amount of 0.01 to 1% by mass. The above-mentioned oral composition.
[4]
The oral composition according to any one of [1] to [3], which is a dentifrice composition.

According to the present invention, the oral cavity containing allantoin or tranexamic acid, which has excellent appearance stability by suppressing coloring and discoloration of the pharmaceutical product even when stored at a high temperature for a long period of time, and has a good taste and high palatability by suppressing sarcasm. Composition can be provided. This oral composition has an anti-inflammatory effect due to allantoin or tranexamic acid, and is effective for prevention or suppression of periodontal diseases such as gingival inflammation.

The oral composition of the present invention comprises (A) one or more selected from allantoin and tranexamic acid, (B) one or more selected from compounds having an aldehyde group and mentoflan, and (C) weight average molecular weight 1, It contains 000 or more and 20,000 or less polyacrylates, and (C) / (A) has a mass ratio of 0.1 to 21.

The component (A) is allantoin and tranexamic acid, and either one may be used alone or both may be used in combination. These are anti-inflammatory agents that have an amino group as a common structure.
Commercially available products can be used. For example, allantoin is a trade name manufactured by Merck & Co., Ltd .; RonaCare Allantoin, a product manufactured by Permakem Asia Co., Ltd., and tranexamic acid is manufactured by Kyowa Pharma Chemical Co., Ltd. Products and the like can be used.
The blending amount of the component (A) is preferably 0.005 to 1% (mass%, the same applies hereinafter) of the entire composition, and more preferably 0.01 to 0.5%. The larger the blending amount, the more the anti-inflammatory effect can be obtained, but 1% or less is preferable from the viewpoint of the discoloration suppressing effect. If it exceeds 1%, the formulation may turn yellow to brown over time.

The component (B) is mentoflan, a compound having an aldehyde group. These are fragrance components, and both can be used in combination. The component (B) has an effect of suppressing the expression of its own sarcasm generated by the combination of the component (C). It also has the effect of suppressing the sarcasm generated by the compounding components other than the component (C).
The component (B) is, for example, trans-2-hexenal, phenylacetaldehyde, propanal, citral, ethylvanillin, synnamic aldehyde, mentoflan, etc., particularly from the viewpoint of suppressing discoloration of the preparation, and among them, trans-2-hexenal. , Phenylacetaldehyde, citral, mentholan are preferred.
As the component (B), one type may be used alone, or two or more types may be used in combination in terms of exhibiting the effect.
The component (B) may be a mixture isolated from an essential oil or a synthetic one, or may be blended in a state of being contained in the essential oil without being isolated from the essential oil. For example, peppermint containing mentholan. Oil can be blended.
As the component (B), commercially available products such as those manufactured by Inoue Fragrance Mfg. Co., Ltd., Toyoda Fragrance Co., Ltd., and Hasegawa Fragrance Co., Ltd. can also be used.

The blending amount of the component (B) is preferably 0.0001 to 0.5%, more preferably 0.0005 to 0.1% of the entire composition. The larger the amount, the better the taste and the sarcasm is suppressed, but 0.5% or less is preferable from the viewpoint of the discoloration suppressing effect.

The component (C) is a polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less. The component (C) is a discoloration inhibitor, and exerts a discoloration inhibitory action of suppressing the coloring and discoloration of the pharmaceutical product caused by the combined use of the components (A) and (B) over time.
The weight average molecular weight (Mw) of the polyacrylate is 1,000 or more and 20,000 or less, preferably 1,000 to 10,000. When the weight average molecular weight is 1,000 or more, the discoloration suppressing effect can be sufficiently obtained. When it is 20,000 or less, the discoloration suppressing effect can be sufficiently ensured. If it exceeds 20,000, the discoloration suppressing effect is lowered, and the pharmaceutical product may turn yellow to brown over time.
The weight average molecular weight was measured by GPC (gel permeation chromatography) under the method and measurement conditions described in Japanese Patent No. 5740859 (the same applies hereinafter). Specifically, it is shown below.
Method for measuring weight average molecular weight;
The weight average molecular weight is a value measured using a gel permeation chromatograph / multi-angle laser light scattering detector (GPC-MALLS), and the conditions are as follows.
Mobile phase: 0.3M NaClO ₄
NaN ₃ aqueous solution column: TSKgelα-M 2 pre-columns: TSKguardcolumn α
Standard substance: Polyethylene glycol

The polyacrylate of the component (C) is preferably a linear polyacrylate from the viewpoint of the effect of suppressing discoloration. As the salt, a monovalent salt is preferable, an alkali metal salt or an ammonium salt is more preferable, an alkali metal salt such as a sodium salt or a potassium salt is more preferable, and a sodium salt is particularly preferable.
As such a polyacrylate, a commercially available product sold by Polyscience Co., Ltd. or Toagosei Co., Ltd. can be used. Specifically, as commercially available products, sodium polyacrylate (Mw: 1,000); linear, manufactured by Polyscience, sodium polyacrylate (Mw: 6,000); linear, Toa Synthetic Co., Ltd. , Julimer AC-10NP, AC-10NPD, Aron T-50, sodium polyacrylate (Mw: 9,000); linear, manufactured by Polyscience, sodium polyacrylate (Mw: 20,000); direct Chain-shaped, manufactured by Toa Synthetic Co., Ltd., Aron A-20UN, etc. can be used.
The polyacrylate of the component (C) has a lower weight average molecular weight than the crosslinked polyacrylate of the binder usually used for dentifrices, and is different from the polyacrylate known as a binder. Is different. When a polyacrylic acid salt other than the component (C) is used instead of the component (C), or when polyacrylic acid in the form of a salt is used, the discoloration of the preparation cannot be suppressed and the discoloration suppressing effect is inferior.

The blending amount of the component (C) is preferably 0.01 to 1%, more preferably 0.05 to 0.5% of the entire composition. When the blending amount is 0.01% or more, the discoloration suppressing effect can be sufficiently obtained. When it is 1% or less, the peculiar sarcasm caused by the component (C) itself is sufficiently suppressed, and a good taste can be maintained.

In the oral composition of the present invention, (C) / (A) indicating the quantitative ratio of the component (A) to the component (C) is 0.1 to 21 as a mass ratio, preferably 0.5 to. It is 15. When the mass ratio of (C) / (A) is within the above range, sarcasm is suppressed and an excellent discoloration suppressing effect can be obtained. If it is less than 0.1, the discoloration suppressing effect is inferior, the preparation turns yellow to brown over time, and if it exceeds 21, the sarcasm of the component (C) itself cannot be suppressed, the taste deteriorates, and the palatability deteriorates. ..

The oral composition of the present invention can be prepared as a dentifrice, a mouthwash, a coating agent, a patch, etc., but is particularly suitable as a dentifrice, a mouthwash, especially a dentifrice, and is a dentifrice composition. Is preferable. The dosage form can be in the form of liquid, liquid, paste or the like, and the dentifrice is preferably a dentifrice, a liquid dentifrice, a liquid dentifrice, a dentifrice or the like, and particularly preferably a dentifrice. Further, in addition to the above components, other optional components according to the intended use, dosage form and the like can be appropriately blended as long as the effects of the present invention are not impaired. Specifically, in dentifrices, surfactants, abrasives, thickeners, binders, and if necessary, sweeteners, preservatives, pigments, known oral flavors other than the component (B), active ingredients, etc. Can be blended.

As the surfactant, an anionic surfactant and a nonionic surfactant may be blended.
Examples of the anionic surfactant include an alkyl sulfate having an alkyl group having 12 to 14 carbon atoms, particularly an alkyl group having 12 carbon atoms, an acyl amino acid salt, an acyl taurine salt and the like. The acyl groups of the acyl amino acid salt and the acyl taurine salt each have preferably 12 to 14 carbon atoms, and more preferably 12 carbon atoms. Specific examples of the alkyl sulfate include lauryl sulfate and myristyl sulfate. Examples of the acyl amino acid salt include acyl glutamate such as lauroyl glutamate and myristyl glutamate, and acyl sarcosine salt such as lauroyl sarcosine salt. Examples of the acyl taurine salt include lauroyl methyl taurine salt and the like. The salt is preferably an alkali metal salt such as a sodium salt or a potassium salt. These can be used alone or in combination of two or more, but alkyl sulfates, acylsarcosine salts, and acyltaurine salts are particularly preferable. Among them, an anionic surfactant having a hydrocarbon group (lauryl group) having 12 carbon atoms is preferable, and in particular, an alkyl sulfate (sodium salt) is more comfortable to use than other surfactants in terms of dispersibility of the preparation. It is more preferable because it is excellent in.
Examples of the nonionic surfactant include polyoxyethylene alkyl ether, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene hydrogenated castor oil, glycerin ester polyoxyethylene ether, sucrose fatty acid ester, and alcoholol. Examples include amide and glycerin fatty acid ester. Of these, polyoxyethylene alkyl ether and polyoxyethylene hydrogenated castor oil are preferably used in terms of solubilization and stable blending of fragrance components. The polyoxyethylene alkyl ether preferably has an alkyl chain having 14 to 20 carbon atoms, and preferably has an average number of moles of ethylene oxide added of 3 to 30. The polyoxyethylene hydrogenated castor oil preferably has an average number of moles of ethylene oxide added of 10 to 100. In particular, when blended in a dentifrice composition, the average number of moles of ethylene oxide added is preferably 10 to 30.

Polishing agents include silica-based abrasives such as crystalline silica, amorphous silica, silica gel, and aluminosilicate, zeolite, calcium hydrogen phosphate anhydride, calcium hydrogen phosphate dihydrate, calcium pyrophosphate, calcium carbonate, and water. Examples thereof include aluminum oxide, alumina, magnesium carbonate, magnesium ferric phosphate, zirconium silicate, calcium tribasic phosphate, hydroxyapatite, calcium tetraphosphate, and synthetic resin-based abrasives. The blending amount of the abrasive is usually 5 to 70%, particularly 10 to 50% of the total composition.

Examples of the viscous agent include sugar alcohols such as sorbitol, xylit and erythritol, and polyhydric alcohols such as propylene glycol, butylene glycol, glycerin and polyethylene glycol. The blending amount of the thickener is usually 0 to 70%, particularly 3 to 50% of the total composition.

As the binder, an organic or inorganic binder can be blended. Specifically, organic viscosities such as cellulose derivatives such as sodium carboxymethyl cellulose, methyl cellulose and hydroxymethyl cellulose, gums such as alginic acid derivatives and xanthan gum, carrageenan, polyvinyl alcohol, and sodium polyacrylate having a higher weight average molecular weight than the component (C). Examples thereof include an agent, a thickening silica, and an inorganic binder such as a thickening aluminum silica. Among them, an inorganic binder, particularly a thickening silica, is preferable from the viewpoint of suppressing discoloration and odor of the preparation. The blending amount of the binder is usually 0.1 to 10% by mass, particularly 0.1 to 5% of the total composition.

Examples of the sweetener include sodium saccharin and the like.
Examples of the preservative include benzoates such as sodium benzoate and paraoxybenzoic acid esters such as methylparaben, ethylparaben and butylparaben.
Examples of the pigment include titanium oxide as a pigment such as edible pigments such as brilliant blue and tartrazine.

Any active ingredient (medicinal ingredient) is, for example, a bactericidal or antibacterial agent such as chlorohexidine, triclosan, isopropylmethylphenol, cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, zinc gluconate, zinc citrate, ethanehydroxydiphos. Toothstone preventive agents such as phonate, glycyrrhizic acid and its salts, anti-inflammatory agents such as epsilon aminocaproic acid, enzyme agents such as dextranase, mutanase and lysoteam chloride, vitamins such as ascorbic acid and tocopherol acetate, sodium chloride and the like. Examples include astringents, hypersensitivity inhibitors such as aluminum lactate and strontium chloride, and fluorides such as sodium fluoride, sodium monofluorophosphate and stannous fluoride. These can be used in effective amounts within a pharmaceutically acceptable range.

Hereinafter, the present invention will be specifically described with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. In the following examples,% indicates mass% unless otherwise specified.

[Examples, comparative examples]
Toothpaste compositions (dentifrices) having the compositions shown in Tables 1 to 9 were prepared by a conventional method, and these were used as test dentifrice compositions and evaluated by the following methods. The results are also shown in the table.

(1) Evaluation method of appearance stability (discoloration suppressing effect) of the pharmaceutical product The dentifrice composition is a laminated tube container (LDPE55 / PET12 / LDPE20 / white LDPE60 / EMAA20) having a diameter of 26 mm and the innermost layer being made of linear low-density polyethylene. / AL10 / EMAA30 / LDPE20 / LLDPE30 (manufactured by Dai Nippon Printing Co., Ltd.) was filled with 50 g, stored in a constant temperature bath at 60 ° C. for 1 month, and then returned to room temperature. The appearance (degree of discoloration) of the formulation when the dentifrice composition is extruded from the laminated tube container is suppressed by the following evaluation criteria using the dentifrice composition of the same composition stored at -5 ° C for 1 month as a control product. The effect was evaluated. The dentifrice composition immediately after preparation was white.
Evaluation Criteria for Suppressing Discoloration Effect ◎: No color change compared to control product ○: Almost no color change compared to control product △: Color change (yellow to browning) compared to control product Yes ×: Color change (yellow to brown) is remarkable compared to the control product.

(2) Evaluation method of taste (sarcasm) 10 subjects put 1 g of dentifrice composition on a toothbrush and brushed for 3 minutes to clean the oral cavity. Sensory evaluation was made with. The average score of 10 people was calculated, and the taste (no sarcasm) was evaluated according to the following evaluation criteria.
Taste (no sarcasm) rating criteria 4 points: No sarcasm in the oral cavity 3 points: Almost no sarcasm in the oral cavity 2 points: Slightly sarcasm in the oral cavity 1 point: Very sarcasm in the oral cavity Evaluation criteria for the taste (no sarcasm) ◎: Average score 3.5 points or more and 4.0 points or less ○: Average score 3.0 points or more and less than 3.5 points △: Average score 2.0 points or more 3.0 Less than points ×: Average points 1.0 points or more and less than 2.0 points

Details of the raw materials used are shown below.
(A) Ingredients Allantoin Product name: RonaCare Allantoin, manufactured by Merck Co., Ltd. Tranexamic acid manufactured by Kyowa Pharma Chemical Co., Ltd. (B) Ingredients Trans-2-hexenal Co., Ltd. Citral Hasegawa Fragrance Co., Ltd. Mentofran Toyoda Fragrance Co., Ltd. (C) Ingredient Sodium polyacrylate (Mw: 1,000)
Linear, Polyscience Sodium Polyacrylate (Mw: 6,000)
Linear, trade name; Julimer AC-10NP, Toagosei Co., Ltd. Sodium polyacrylate (Mw: 9,000)
Linear, Polyscience Sodium Polyacrylate (Mw: 20,000)
Linear, trade name; Aron A-20UN, Toagosei Co., Ltd. Sodium polyacrylate (Mw: 300,000) (comparative product)
Made by Polyscience

Claims

(A) One or more selected from allantoin and tranexamic acid,
It contains (B) one or more selected from compounds having an aldehyde group and mentoflan, and (C) polyacrylate having a weight average molecular weight of 1,000 or more and 20,000 or less, and (C) / (A) is the mass. Oral compositions having a ratio of 0.1 to 21.
The oral composition according to claim 1, wherein the component (B) is selected from trans-2-hexenal, phenylacetaldehyde, citral and mentoflan.
The oral cavity according to claim 1 or 2, which contains 0.005 to 1% by mass of the component (A), 0.0001 to 0.5% by mass of the component (B), and 0.01 to 1% by mass of the component (C). Composition for.
The oral composition according to any one of claims 1 to 3, which is a dentifrice composition.